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Abstract Topical antiaging therapies provide noninvasive delivery of active therapeutics. Exosomes, or extracellular nanovesicles, and peptides, small strings of amino acids, have shown promise as topical therapies in early trials, but neither is FDA approved. This review aims to elucidate the current and future landscape of topical exosomes and peptides as therapeutics for skin rejuvenation. A literature search was conducted using the keywords “peptides” OR “exosomes” AND “skin” OR “rejuvenation.” Primary endpoints included mechanisms of action in humans or live animals as well as clinical data supporting the use of exosomes or peptides topically for skin rejuvenation or wound healing. Secondary endpoints were safety, side effects, and efficacy. The articles were collected, organized, and sorted using the Covidence software (Melbourne, Australia) for systematic review. Nine articles evaluating topical application of exosomes and 9 of peptides met inclusion criteria. Topical exosomes were found to increase collagen deposition, accelerate wound healing, and improve overall cosmesis. Several clinical trials are currently underway. Topical peptides were found to improve appearance of fine lines and wrinkles, elasticity and viscoelasticity, skin texture, skin thickness, and the potential for accelerated wound healing. Peptides are quite common in “cosmeceutical” products, and several patents have been filed for topical peptide products aimed at increasing skin rejuvenation. This could indicate a movement toward pursuing FDA approval. The future of topical exosome and peptide products for the purpose of skin rejuvenation appears promising. Preliminary data from the studies reviewed here indicates that these products have the potential to be safe and effective. Level of Evidence: 3