There is no first-line treatment for vitiligo, a skin disease characterized by a lack of melanin produced by the melanocytes, resulting in an urgent demand for new therapeutic drugs capable of stimulating melanocyte functions, including melanogenesis. In this study, traditional medicinal plant extracts were tested for cultured human melanocyte proliferation, migration, and melanogenesis using MTT, scratch wound-healing assays, transmission electron microscopy, immunofluorescence staining, and Western blot technology. Of the methanolic extracts,Lycium shawiiL. (L. shawii) extract increased melanocyte proliferation at low concentrations and modulated melanocyte migration. At the lowest tested concentration (i.e., 7.8 μg/mL), theL. shawiimethanolic extract promoted melanosome formation, maturation, and enhanced melanin production, which was associated with the upregulation of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2 melanogenesis-related proteins, and melanogenesis-related proteins. After the chemical analysis andL. shawiiextract-derived metabolite identification, thein silicostudies revealed the molecular interactions between Metabolite 5, identified as apigenin (4,5,6-trihydroxyflavone), and the copper active site of tyrosinase, predicting enhanced tyrosinase activity and subsequent melanin formation. In conclusion,L. shawiimethanolic extract stimulates melanocyte functions, including melanin production, and its derivative Metabolite 5 enhances tyrosinase activity, suggesting further investigation of theL. shawiiextract-derived Metabolite 5 as a potential natural drug for vitiligo treatment.