In this study, derivatives of trimethoxybenzene were investigated as inhibitors of melanogenesis. We examined the effects of methyl 3,4,5-trimethoxybenzoate (MTB), ethyl 3,4,5trimethoxybenzoate (ETB), methyl 3,4,5-trimethoxycinnamate (MTC), and ethyl 3,4,5-trimethoxycinnamate (ETC). First, the inhibitory effects of these agents on melanin production were evaluated using α-melanocyte-stimulating hormone (α-MSH)stimulated B16F10 melanoma cells. We found that all derivatives decreased α-MSH-induced melanin production in B16F10 melanoma cells; ETC showed a strong inhibitory effect at half of the concentration of the other derivatives. As tyrosinase is considered a key enzyme of melanogenesis, we also examined whether the derivatives inhibited tyrosinase activity. MTC and ETC reduced mushroom tyrosinase activity and expression levels of α-MSH-induced B16F10 cellular tyrosinase protein. Inhibitory effects of all derivatives on α-MSH-induced B16F10 cellular tyrosinase activity were shown in a dose-dependent manner. Additionally, the derivatives were exposed to diphenylpicrylhydrazyl free radical to examine their antioxidant characteristics. All derivatives showed considerable antioxidant activity, which was 2-fold higher than that of arbutin. In conclusion, the trimethoxybenzene derivatives, including MTB, ETB, MTC, and ETC exerted anti-melanogenic and antioxidant effects on α-MSHstimulated melanogenesis, demonstrating their potential for use as novel hypopigmenting agents and antioxidants.