Background: Hyperpigmentation is a skin disorder, which is caused by an excess production of melanin. The reduction in melanin content without causing undesirable effects is required for the treatment of hyperpigmentation. Sericin is increasingly used as a hyperpigmentation treatment because of its antityrosinase activity. However, the various methods of sericin extraction have an effect on the composition and biological properties. The purpose of this study was to investigate the antioxidant and anti-melanogenic properties of sericin using different extraction methods including acid, base, heat, and urea extraction. Methods: The chemical properties of extracted sericin were assessed in terms of amino acid components, thermal behavior, and UV-vis absorption. The inhibitory effects of sericin on melanogenesis were explored by determining the melanin content and cellular tyrosinase activity in B16F10 cells.Results: Sericin from urea extraction provided different properties when compared with the other extraction methods. Our results indicate that urea-extracted sericin reduced the melanin content and cellular tyrosinase activity more effectively than the other extraction methods. Interestingly, the potential anti-melanogenic activity was more effective than kojic acid, a depigmenting agent used to treat hyperpigmentation.Conclusions: Our results present the potential inhibitory effect of urea-extracted sericin on melanogenesis. Our results support the therapeutic potential of urea-extracted sericin in the treatment of hyperpigmentation and its complications.