Recent studies of our newly developed synthetic collagen-like hexapeptide have shown that it enhances cultured cell adhesion and differentiation and improves the morphology of ex vivo skin. Consequently, we were interested in further investigating the effects of the collagen-like peptide on the skin. We performed different immunostaining studies on ex vivo human skin samples treated with the collagen-like peptide at 1% in time course studies. Our research also included comparative studies with vitamin C (often used as a positive control for enhancing collagen synthesis). The results showed that application of the collagen-like peptide to the skin enhanced synthesis of many extracellular matrix (ECM) molecules and that this effect was observed very early in some ECM molecules such as laminin 5, collagen 111, and collagen IV The expression of the other molecules was increased after different times of application of the collagen-like peptide. Interestingly, comparative studies with vitamin C showed that the synthesis response of some ECM molecules such as laminin 5, collagen 111 and collagen IV was more rapid after the administration of the collagen-like peptide than through vitamin C administration. Our results also revealed that after a longer treatment period, both active ingredients stimulated ECM molecule synthesis to a similar degree, with the exception of some molecules that remained superiorafterpeptide administration, such as collagen IV and beta 1 integrin. These histological studies demonstrate the remarkable and rapid effect of the collagen-like peptide on stimulating ECM molecule synthesis and suggest wide application for the peptide in antiaging and photoaging skin care products.