The rise of peptides in skincare: A scientific perspective

Peptides have emerged as a powerhouse skincare ingredient, captivating both consumers and aesthetic healthcare professionals. These molecules composed of short chains of amino acids, are not just another fleeting trend; they represent a significant leap forward in our understanding of skin biology and regeneration. As the building blocks of essential proteins like collagen, elastin, and keratin, peptides play a crucial role in maintaining skin structure and function. Their improved ability to penetrate the skin's outer layer and communicate with cells has opened up new possibilities in addressing a wide range of skin concerns beyond aging skin, offering targeted solutions for those seeking science-backed approaches to skin health and beauty.
 
WHAT ARE PEPTIDES?
Peptides are short chains of amino acids, typically consisting of 2–50 amino acids, linked by peptide bonds. [1] They can function as hormones, neurotransmitters and immune messengers, and they also appear as fragments of structural proteins such as collagen, elastin, and keratin, which are essential for skin structure and function. This dual role - structural and signalling - is what makes peptides so attractive as cosmeceutical ingredients. [2] 

BODY´S OWN PEPTIDES: BRAIN, BODY AND SKIN
The exact number of endogenous peptides in the brain, body, and skin is unknown, but we know they form dense communication networks across multiple systems. In the brain, neuropeptides such as oxytocin, vasopressin, endorphins, and enkephalins are involved in mood regulation, social behaviour, and pain modulation. In the rest of the body, hormone peptides like insulin, glucagon, and growth hormone regulate glucose metabolism, energy balance, growth, and tissue repair, and are even explored off‑label in some regenerative medicine settings.

In the skin, collagen peptides provide structural support and elasticity, while elastin peptides contribute to elasticity and resilience; together with cytokine‑like peptides and antimicrobial peptides (AMPs), they help coordinate barrier function, immune defence, pigmentation, and wound healing. This endogenous peptide “language” is what cosmetic peptide design tries to mimic or amplify.
 
INCREASING POPULARITY IN SKINCARE
The global peptide‑based cosmetics market has grown steadily and is projected to continue this trend, driven by demand for more targeted, “active” skincare and by advances in peptide synthesis and delivery. Asia‑Pacific is expected to show especially strong growth, while North America and Europe currently lead in innovation and early adoption. From an R&D point of view, peptides are attractive because they combine high specificity and relatively low immunogenicity with the ability to be fine‑tuned at the sequence level.

POTENTIAL BENEFITS OF PEPTIDES IN SKINCARE
1. Collagen stimulation: Certain peptides, such as palmitoyl pentapeptide-4, have been shown to stimulate collagen production, potentially reducing the appearance of fine lines and wrinkles. [6]
2. Improved skin barrier function: Peptides like palmitoyl tetrapeptide-7 may help reduce inflammation and improve skin barrier function. [7]
3. Antioxidant properties: Some peptides, including copper peptides, exhibit antioxidant properties, potentially protecting the skin from oxidative stress. [8]
4. Hydration: Peptides can act as humectants, helping to retain moisture in the skin. [9]

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MECHANISMS OF ACTION
Most cosmetic peptides are grouped by their function in the skin rather than their origin. The main classes are signal (messenger/matrikine) peptides, carrier peptides, neurotransmitter‑inhibiting/neuromodulating peptides, enzyme‑inhibitory and antimicrobial/antioxidant peptides, plus several emerging subgroups.

1. SIGNAL PEPTIDES
Signal peptides (including matrikines) send biochemical “instructions” to cells, particularly fibroblasts, to make more extracellular matrix (ECM) components or remodel damaged tissue. [3] Many are fragments of collagen or other matrix proteins that naturally appear during injury or remodelling and tell the skin it is time to repair. 

Palmitoyl pentapeptide‑4 (Pal‑KTTKS, Matrixyl)  [4]
▌Mechanism: Mimics a collagen fragment and stimulates collagen I, III, and IV synthesis.
▌Penetration: Palmitoylation increases lipophilicity and improves skin penetration.
▌Efficacy: Increases ECM components in vitro and improves wrinkles clinically when used at effective concentrations.

Palmitoyl tripeptide‑1 (Pal‑GHK) [5]
▌Mechanism: Collagen‑derived matrikine that activates TGF‑β signalling and promotes ECM production (collagen, elastin, GAGs).
▌Penetration: Enhanced by the palmitoyl group.
▌Efficacy: Multifunctional, targeting several aspects of skin ageing, though long‑term independent data are still relatively limited.
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Palmitoyl tetrapeptide‑7
▌Mechanism: Reduces IL‑6 to help suppress inflammation and prevent collagen breakdown, while promoting laminin IV/V and collagen VII synthesis at the dermal–epidermal junction.
▌Penetration: Good, due to palmitoylation and moderate size.
▌Efficacy: In vitro IL‑6 reduction and clinical data showing less redness and improved firmness, especially in combination formulas such as Matrixyl 3000.

Matrixyl 3000 (Pal‑GHK + Palmitoyl tetrapeptide‑7)
▌Mechanism: A patented matrikine complex that signals fibroblasts to boost collagen I and IV, fibronectin, and GAGs while suppressing IL‑6‑driven inflammation.
▌Efficacy: In vitro collagen increases up to several‑fold and clinical trials showing meaningful wrinkle reduction after a few months.

Palmitoyl tripeptide‑5
▌Mechanism: Mimics a thrombospondin‑1 sequence to activate TGF‑β, stimulating collagen I/III synthesis and inhibiting MMP‑1 and MMP‑3, thereby combining ECM build‑up with protection against enzymatic degradation.
▌Efficacy: In vitro data show strong ECM increases; clinical studies report wrinkle reduction after around 12 weeks.

Palmitoyl tripeptide‑38
▌Mechanism: A next‑generation matrikine that stimulates multiple ECM components at the dermal–epidermal junction, including collagens I, III, IV, fibronectin, hyaluronic acid, and laminin‑5.
▌Efficacy: In vitro increases in these components after 7 days and clinical improvements in wrinkles and elasticity after around 8 weeks.

Hexapeptide‑9
▌Mechanism: A hybrid neuro/signal peptide that mimics collagen fragments to stimulate collagen I, III, IV, laminin‑5 and integrins, improving dermal–epidermal junction cohesion and firmness.
▌Efficacy: Clinical studies report wrinkle reduction and elasticity improvements after about 4–8 weeks of use.

GEKG (Gly‑Glu‑Lys‑Gly) [7] 
▌Mechanism: A tetrapeptide derived from ECM proteins that significantly induces collagen production at both protein and mRNA level in human dermal fibroblasts.
▌Efficacy: Shown to boost collagen, hyaluronic acid, and fibronectin and up‑regulate genes responsible for ECM formation up to ~2.5‑fold.

RGD‑GHK and sOtx2‑GHK [5]
▌Mechanism: GHK derivatives with additional binding motifs (e.g. RGD) that enhance cell‑surface interaction and receptor targeting.
▌Efficacy: Show superior anti‑oxidative and anti‑apoptotic effects compared with GHK alone, with promising activity for anti‑ageing and wound healing.

Palmitoyl hexapeptide‑12
▌Mechanism: Supports dermal matrix regeneration and firmness, and is associated with activation of longevity‑related genes (Klotho, SIRT1) and autophagy pathways while promoting collagen synthesis and ECM remodelling.
▌Evidence: Preclinical longevity data in fibroblast and ageing models are still relatively early but conceptually interesting.

Oligopeptide‑20
▌Mechanism: Growth‑factor‑mimicking and enzyme‑modulating peptide used especially in K‑beauty to support epidermal renewal and brightening.
 
​2. CARRIER PEPTIDES
Carrier peptides bind and deliver trace metals that are essential cofactors for enzymatic reactions involved in antioxidant defence and tissue repair. [3]​

GHK‑Cu (Copper tripeptide‑1) [3][4] 
▌Mechanism: Chelates copper and transports it into cells, where it supports collagen and elastin synthesis, angiogenesis, antioxidant enzyme activity, and wound healing.
▌Efficacy: Well‑studied in wound healing and increasingly used in anti‑ageing skincare; it also has antioxidant properties, although at high or imbalanced levels copper can be pro‑oxidative.
 
3. NEUROTRANSMITTER-INHIBITING PEPTIDES
These peptides act on neuromuscular or sensory pathways to soften expression lines or reduce stinging, burning, and itch. [3]

Acetyl hexapeptide‑3/8 (Argireline) [4]
▌Mechanism: Inhibits SNARE complex formation at the neuromuscular junction, reducing acetylcholine release and thereby decreasing muscle contraction that contributes to expression lines.
▌Efficacy: Offers modest softening of dynamic wrinkles as a non‑invasive topical option; its effects are temporary and depend on concentration and compliance. Is often compared to botulinum toxin (mode of action), however it´s efficacy isn´t comparable.

Neurosensine (acetyl dipeptide‑1 cetyl ester)
A dipeptide of arginine and tyrosine linked to a cetyl ester.
▌Mechanism: Stimulates the production of endorphins and enkephalins in keratinocytes, which act as natural pain relievers, and modulates TRP‑mediated neurogenic inflammation.
▌Efficacy: Helps create a more protective micro‑environment around nerve endings, making skin less prone to redness, dryness, irritation, and itch, especially in sensitive or reactive skin.

4. ENZYME INHIBITORY, ANTIMICROBIAL AND ANTI-OXIDANT PEPTIDES
Several peptides primarily exert their effects by blocking enzymes, defending against microbes, or modulating oxidative stress.

▌Oligopeptide‑20 (as above) is often positioned as a growth‑factor‑mimic and enzyme‑inhibiting peptide that supports epidermal renewal and brightening.
▌Antimicrobial peptides (AMPs) are part of the innate immune system and help defend against bacteria, fungi, and viruses; synthetic or biomimetic versions are being investigated for acne‑prone and microbiome‑disrupted skin.
▌Antifungal peptides (AFPs) are specialised AMPs that target fungal pathogens and may be relevant for scalp or body care in predisposed individuals.
▌Antioxidant peptides include sequences that directly scavenge reactive oxygen species or up‑regulate endogenous antioxidant systems; copper peptides are a key example, combining carrier and antioxidant functions.

5. SPECIALIZED AND EMERGING PEPTIDE TYPES
Several specialised peptide families that sit at the interface of skincare, regenerative medicine, and longevity.

▌Cell‑penetrating peptides (CPPs) are short, usually cationic peptides rich in arginine and lysine [13] that can cross cell membranes [14] and carry cargo such as proteins, peptides, and nucleic acids into cells. [12][15] This makes them highly attractive as delivery tools for future topical and transdermal actives. [11][12] 
 ▌OS‑01 / Peptide‑14 (senotherapeutic peptide) is designed to target cellular senescence, one of the key hallmarks of skin ageing. In 2D cultures, 3D skin equivalents from older donors, and ex vivo human skin, OS‑01 reduces markers of senescence (including p16 and SASP‑related genes), increases epidermal thickness and collagen expression, and lowers DNA‑methylation‑based biological age of skin by about 2.6 years on average. These data support classifying OS‑01 as a senotherapeutic - more precisely a senomorphic - peptide that helps prevent cells from progressing to a late, pro‑inflammatory senescent state. [16][17]
▌Epithalon is a tetrapeptide associated with telomerase activation and telomere length maintenance in systemic studies; in work by Khavinson et al., Epithalon treatment increased telomere length in blood cells of older patients, positioning it within longevity research rather than classical topical cosmetics.
▌BPC‑157 is a pentadecapeptide known from experimental work in tendon and gut repair; it enhances growth hormone receptor expression in fibroblasts and supports collagen production, with growing interest in broader tissue regeneration and potential skin benefits. [19] 
▌NAD+ is not a peptide but a central coenzyme for energy production, DNA repair, and cellular resilience whose levels decline with age; NAD+ augmentation is explored as a complementary longevity strategy.  [18]

BARRIER, SENSITIVE SKIN AND TEXTURE-FOCUSED PEPTIDES 
Some peptides are best understood through their barrier and sensory effects.

Palmitoyl tetrapeptide‑10
▌Mechanism: A synthetic tetrapeptide acylated with palmitic acid that increases expression of corneodesmosin and filaggrin in reconstructed human epidermis, improving corneocyte adhesion and terminal differentiation.
▌Efficacy: Associated with improved barrier function and reduced perceived sensitivity; supplier data also suggest increased firmness and a “soft‑polish” effect, though independent clinical data on the isolated peptide are still limited.
Neurosensine 
▌Especially relevant for sensitive or redness‑prone skin due to its effects on keratinocyte‑derived endorphins, enkephalins, and neurogenic inflammation pathways.

COLLAGEN-STIMULATING PEPTIDES AND ORAL COLLAGEN 
Topically, signal peptides such as Pal‑KTTKS [3], Pal‑GHK [3], GEKG and complexes like Matrixyl 3000 modulate fibroblast activity and increase the expression and synthesis of collagen and other extracellular matrix components, which can improve the structural integrity and appearance of the skin. 
[1][2] Orally, specific collagen‑derived peptides from bovine and marine sources are absorbed as small di‑ and tripeptides, reach the skin via the circulation, and have been shown to stimulate dermal fibroblasts and increase expression of collagen and other ECM‑related genes in experimental models. Clinical studies report improvements in skin hydration, elasticity and wrinkle parameters after several weeks of oral collagen peptide supplementation. Bovine collagen peptides are typically rich in types I and III, while marine collagen provides mainly type I and is often reported to have high bioavailability; plant‑based “collagen boosters” do not contain collagen but supply co‑factors such as vitamin C, silica and amino acids that support the body’s own collagen synthesis. In powder form, hydrolysed collagen peptides are easy to mix into foods or beverages and show better absorption than intact gelatin.
   
MORE PEPTIDES
1. Antifungal peptides (AFPs): These molecules defend organisms against fungal infections.
2. Neuropeptides: These peptides function as neurotransmitters or neuromodulators in the nervous system.
3. Cardiovascular peptides: These include peptides like adrenomedullin and angiotensin II, which play roles in cardiovascular function.
4. Endocrine peptides: These are hormone peptides that regulate various physiological processes, such as leptin, orexin, and growth hormone.
5. Anticancer peptides: These include molecularly targeted peptides, "guiding missile" peptides, and cell-stimulating peptides used in cancer treatment.
6. Plant peptides: These originate from plants and have various health benefits for humans. They can be incoroprated in skincare formulations.
8. Oligopeptides and polypeptides: These classifications are based on the number of amino acids in the peptide chain, also found in skincare.
9. Ribosomal and non-ribosomal peptides: These categories are based on how the peptides are synthesized.
 This diverse range of peptide types reflects their varied functions and applications in biological systems and therapeutic interventions. 
 
PEPTIDE FLOODING
“Peptide flooding” is used on social media to describe layering several peptide serums or very high peptide concentrations in one routine, assuming that more products mean more results. In reality, cosmetic peptides act via specific receptors and signalling pathways and have optimal concentration windows; once these targets are engaged, extra layers mostly add formulation load, not extra biology. Penetration and cell‑surface interaction are usually the limiting factors, and these are shaped by peptide sequence, charge, lipid modification (e.g., palmitoylation), and delivery system rather than the sheer number of bottles used. Current evidence supports well‑designed multi‑peptide products that combine complementary mechanisms (e.g., matrikines, which are tiny signal/messenger peptides that tell your skin to repair itself, for extracellular matrix support; senotherapeutic peptides for high‑senescence; anti‑inflammatory or barrier peptides for sensitivity) within a barrier‑supportive vehicle, instead of stacking multiple peptide serums. [21] 
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CHALLENGES 

One of the challenges with peptides in skincare is their skin permeability. For example, most anti-wrinkle peptides are not ideal candidates for skin permeation, and enhancement methods are often necessary to increase their permeability and effectiveness. [5] Researchers are exploring ways to improve peptide delivery and efficacy, such as designing novel targeting peptide motifs to enhance the interaction between cosmetic peptides and the cell surface. [5] Various methods have been developed to improve peptide penetration into the skin, including chemical modification, use of penetration enhancers, and encapsulation in nanocarriers. [10]  

Peptides are powerful tools, but they’re not “easy” ingredients. How well they work depends on the exact sequence of amino acids, the formula around them, how stable they are, the dose, how they are delivered into the skin, and the person’s own skin biology. Many peptides can break down quickly (for example by oxidation or skin enzymes), so they need smart formulation, protective packaging, and careful manufacturing, which is still challenging for some of the more complex types.

For users, the key questions are: which peptide(s), in what vehicle (formula), at what dose, for which skin concern. When used thoughtfully in this way, peptides can meaningfully contribute to skin regeneration, barrier health, comfort, and visible ageing outcomes. Always consult a qualified healthcare professional to determine what the most suitable approach is for your needs and  goals. 
 
Take care
Anne-Marie
 
References:
[1] Edgar, S., Hopley, B., Genovese, L. et al. Effects of collagen-derived bioactive peptides and natural antioxidant compounds on proliferation and matrix protein synthesis by cultured normal human dermal fibroblasts. Sci Rep 8, 10474 (2018). https://doi.org/10.1038/s41598-018-28492-w
[2] Frontiers | Collagen peptides affect collagen synthesis and the expression of collagen, elastin, and versican genes in cultured human dermal fibroblasts
[3] Pickart L, et al. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. doi:10.1155/2015/648108.
[4] Draelos, Z. D. (2007). What are cosmeceutical peptides? Dermatology Times, 28(11). Retrieved from https://www.dermatologytimes.com/view/what-are-cosmeceutical-peptides
[5] He B, Wang F, Qu L. Role of peptide-cell surface interactions in cosmetic peptide application. Front Pharmacol. 2023 Nov 13;14:1267765. doi: 10.3389/fphar.2023.1267765. PMID: 38027006; PMCID: PMC10679740.
[6] Binder L, et al. Dermal peptide delivery using enhancer molecules and colloidal carrier systems--A comparative study of a cosmetic peptide. Int J Pharm. 2018;557:36-46. doi:10.1016/j.ijpharm.2018.08.019.
[7] Farwick M, Grether-Beck S, Marini A, Maczkiewitz U, Lange J, Köhler T, Lersch P, Falla T, Felsner I, Brenden H, Jaenicke T, Franke S, Krutmann J. Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof. Exp Dermatol. 2011 Jul;20(7):602-4. doi: 10.1111/j.1600-0625.2011.01307.x. PMID: 21692860.
[8]  Bae, S. H., et al. (2020). "Copper peptides as a potential therapeutic agent for skin aging." Journal of Cosmetic Dermatology, 19(9), 2245-2252. doi:10.1111/jocd.13435.
[9]  Zhao, Y., et al. (2019). "Peptides and Proteins as Skin Moisturizers." Cosmetics, 6(3), 32. doi:10.3390/cosmetics6030032.
[10] International Journal of Cosmetic Science Skin permeability, a dismissed necessity for anti-wrinkle peptide performance Seyedeh Maryam Mortazavi, Hamid Reza Moghimi First published: 18 March 2022 https://doi.org/10.1111/ics.12770
[11] Lindgren, M., Hällbrink, M., Prochiantz, A., & Langel, Ü. (2000). Cell-penetrating peptides. Trends in Pharmacological Sciences, 21(3), 99-103.
[12] Tripathi, P. P., Arami, H., Banga, I., Gupta, J., & Gandhi, S. (2018). Cell penetrating peptides in preclinical and clinical cancer diagnosis and therapy. Oncotarget, 9(98), 37252-37267.
[13] Chu, D., Xu, W., Pan, R., Ding, Y., Sui, W., & Chen, P. (2015). Rational modification of oligoarginine for highly efficient siRNA delivery: structure-activity relationship and mechanism of intracellular trafficking of siRNA. Nanomedicine: Nanotechnology, Biology and Medicine, 11(2), 435-446.
[14] Frankel, A. D., & Pabo, C. O. (1988). Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 55(6), 1189-1193.
[15] Guidotti, G., Brambilla, L., & Rossi, D. (2017). Cell-Penetrating Peptides: From Basic Research to Clinics. Trends in Pharmacological Sciences, 38(4), 406-424.
[16] Zonari, A., et al. (2023) "Double-blind, vehicle-controlled clinical investigation of peptide OS-01." Journal of Cosmetic Dermatology. doi:10.1111/jocd.16242.
[17] Kirkland, J. L., et al. (2017). "Cellular Senescence: A Key Regulator of Aging." *Nature Reviews Molecular Cell Biology*, 18(7), 473-485. doi:10.1038/nrm.2017.30.
[18] Fang, E. F., et al. (2019). NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nature Communications, 10(1), 5284.
[19] Chang CH, Tsai WC, Hsu YH, Pang JH. Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts. Molecules. 2014 Nov 19;19(11):19066-77. doi: 10.3390/molecules191119066. PMID: 25415472; PMCID: PMC6271067.
[20] Resende, Diana I. S. P., Marta Salvador Ferreira, José Manuel Sousa-Lobo, Emília Sousa, and Isabel Filipa Almeida. 2021. "Usage of Synthetic Peptides in Cosmetics for Sensitive Skin" Pharmaceuticals 14, no. 8: 702.
[21] Badilli U, Inal O. Current Approaches in Cosmeceuticals: Peptides, Biotics and Marine Biopolymers. Polymers (Basel). 2025 Mar 18;17(6):798. doi: 10.3390/polym17060798. PMID: 40292641; PMCID: PMC11946782.

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