Here, we investigated the anti-oxidant and anti-melanogenic effects of pomelo peel essential oil (PPEO) from pomelo cv. Guan Xi. The volatile chemical composition of PPEO was analyzed with gas chromatography-mass spectrometry (GC/MS). The most abundant component of PPEO was limonene (55.92%), followed by ?-myrcene (31.17%), and ?-pinene (3.16%). PPEO showed strong anti-oxidant activities against 1,1-diphenyl-2-picryhydrazyl (DPPH) (,2,2`-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) (, and superoxide anion free radicals. Based on the B16 melanoma cell system, the effects of PPEO on the viability and morphology of B16 cells and the production of melanin were evaluated. The results revealed that PPEO at concentrations below 50 ?g/mL could decrease the melanin content without affecting cell viability and morphology. Intracellular tyrosinase (TYR) activity and Western blot analysis showed that PPEO could down-regulate the expression level of TYR in B16 cells and dose-dependently inhibit TYR activity (by a maximum of 64.54%). Meanwhile, the main active components responsible for the effect are citral and ?-myrcene. In conclusion, PPEO has good anti-oxidant and anti-melanogenic activity, and thus can be widely used as a natural antioxidant in the food, pharmaceutical, and cosmetic industries.