Rice is one of the plants proven to possess antioxidant, anti-inflammatory, anti-proliferative, and whitening properties, making it one of the most beneficial plants in this regard. This study aimed to introduce a novel natural cosmetic and pharmaceutical product based on rice callus as a source of active ingredients that can inhibit skin melanoma cell (B16F10) proliferation and brighten the skin. The 2,4-D hormone at concentrations of 1 µg/mL and 1.5 µg/mL was used to induce rice callus formation. Rice callus extracts were then prepared using aqueous and ethanolic solvents, with a concentration of 1 mg/mL used for characterization tests. To determine the optimal hormone concentration, the phenols/flavonoids, antioxidant activity, proteins, and carbohydrates in the extracts were measured. The optimal concentration of the hormone was found to be 1 µg/mL. Finally, the anti-melanocyte and skin-whitening activity of the extracts was assessed through measurements of their cytotoxicity and inhibition of melanin synthesis-related enzymes. Cellular cytotoxicity measurements revealed that the ethanolic extract induced more cytotoxicity than the aqueous extract, with IC50 values of 566.3 µg/mL for the ethanolic extract and 1327 µg/mL for the aqueous extract. Skin-whitening-related tests demonstrated that the extracts were 1.7 times more effective than arbutin in inhibiting factors that cause hyperpigmentation. The aqueous extract achieved 85% inhibition of melanin biosynthesis at a concentration of 3200 µg/mL, compared to 68% for the ethanolic extract and 50% for arbutin. Based on these findings, rice callus extract can be introduced as a new, effective substance for skin-lightening and anti-melanocyte products in cosmeceutical and pharmaceutical formulations.