The presence of large amounts of bioactive compounds such as saponins and flavonoids in ginseng (Panax ginseng) berry suggests its potential as a functional resource for the food and medical industries, despite the fact that been considered a useless by-products of P. ginseng. In this study, we examined the variations in the antioxidant and anti-melanogenic potential of ginseng berry during the ripening process. We found that fully ripe berry extracts (Go-S3) contained the highest level of antioxidant and anti-melanogenic activities. Phytochemical screening suggested that alterations in polyphenol contents correlated with the variation in bioactive principles of ginseng berry during the ripening process. Furthermore, results obtained by quantitative real-time PCR, western blot, tyrosinase inhibition assay and molecular docking analysis suggested that Go-S3 probably inhibits tyrosinase activity by interacting with copper-coordinating histidines and second shell residues of tyrosinase, resulting in the reduction of melanin production in α-MSH-stimulated B16F10 cells. Taken together, these finding suggest the potential of ginseng berry as a resource for functional applications in the cosmetic industries and demonstrate that fruit ripening stages have profound effects on the pharmaceutical value of ginseng berry