Aim: The aim of this study was to optimize, develop, characterize and evaluate a topical nanobigel (BG) formulation containing Berberine (BRB) that exhibits anti-melanogenic properties. Materials & methods: The Berberine-loaded bigel (BRB@BG) formulation was prepared by homogenously mixing the optimized hydrogel and oleogel. BRB@BG was characterized in vitro and cytotoxicity study was conducted to evaluate its effects on murine skin melanoma B16F10 cell lines. Results: The optimized BRB@BG exhibited uniform texture with nanometric size, desirable spreadability and extrudability, suitable for topical applications. Cytotoxicity studies revealed that BRB@BG had a lower IC50 value (4.84μg/ml) on B16F10 cell lines compared with drug alone. Conclusion: In conclusion, the developed BRB@BG formulation showed good potential as safe and effective topical treatment for hyperpigmentation.