Melasma hyperpigmentation is an acquired disorder predominantly affecting the female population. The present study was conducted to determine the potential of a botanical extract to reduce observable hyperpigmentation. The extract from heartwood of Artocarpus incisus was formulated into nanoemulsions, and the depigmenting efficacy of the formulated nanoemulsion was determined in vivo. HPLC analysis showed that the extract contained artocarpin in an amount of 44.5 ± 0.1% w/w. The extract exhibited melanogenesis inhibition with an IC(50) value of 30.2 ± 2.4 mg/ml, while kojic acid, a well known lightening agent, exhibited an IC(50) of 51.4 ± 5.1 mg/ml. The nanoemulsion containing the extract was then formulated and prepared by the phase inversion technique. The concentration of the extract used was about six times its IC(50). The optimal formula containing 0.02% w/w extract, 41.6% w/w isopropyl myristate, 0.03% w/w α-tocopherol, 5% w/wglyc-eryl monostearate (co-emulsifier), 8% w/w ceteareth-10 (emulsifier), 0.05% triethanolamine, 0.03% w/w carbopol 940, and water adjusted to 100% w/w provided a homogeneous o/w emulsion with a droplet size of 325 ± 15 nm and a polydispersity of 0.31 ± 0.02. The depigmenting efficacy was then observed following topical application of the formulated nanoemulsion to UVB-stimulated hyperpigmented dorsal skin of C57BL/6 mice. A strongly visible decrease in hyperpigmentation was observed after six weeks of treatment with the formulated nanoemulsion. The degree of pigmentation decreased after the application was 84 ± 4 units, while that after the application of the extracted prepared into solution was 51 ± 3 units. The applied areas would return to their original color after treatment was stopped for four weeks.