As aging process continues in human skin, collagen production is reduced and fragmentation is increased, which is initiated by matrix metalloproteinase-1. Elastase is a degrading enzyme present in the dermis, and plays a role in the degradation of the ECM, which contains elastin. We developed natural compounds-peptides derivatives as potential anti-wrinkle agents which combined anti-oxidative small molecule and peptides have an effect on collagenase or elastase active sites. We synthesized 100 natural compounds-peptides derivatives by solid-phase peptide synthesis method. We evaluated anti-wrinkle activities of these natural compounds-peptide derivatives in vitro. Collagen synthesis assay, collagenase activity inhibition assay and elastase activity inhibition assay were performed using human fibroblast. Further efforts to verify their anti-wrinkle activities in vivo and their application for cosmetics are underway.