Antimelanogenic agents from natural sources have been widely investigated. Urolithin A (UA) and B (UB), the main gut microflora metabolites of dietary ellagic acid derivatives, have various bioactivities such as anti-inflammatory and antiaging effects. In this study, the metabolites were found to possess depigmentation efficacy by suppressing tyrosinase activity. Both UA and UB could attenuate melanogenesis in B16 melanoma cells to 55.1 ± 3.8 and 76.4 ± 17.4% of control at noncytotoxic dosage, 10 μM, respectively. UA showed comparable efficacy to positive control, 5 μM of kojic acid treatment (51.2 ± 7.8). RT-PCR results revealed that UA and UB inhibited melanin formation by affecting the catalytic activity of tyrosinase rather than its mRNA expression. Kinetics for UA and UB on tyrosinase activity revealed that their inhibition behavior toward cellular tyrosinase involved competitive inhibition. UA and UB may be potent tyrosinase inhibitors and they possess significant antimelanogenesis ability as novel skin-whitening ingredients.