The effects of wild type and UV-irradiated lemon balm (Melissa officinalis) ethanolic extracts (MOE and UMOE) on melanogenesis in vitro were examined. UMOE showed potent antioxidant activity and significantly inhibited the mushroom and melanocyte tyrosinase activity, and lowered cellular melanin content by 49% at $200{mu}g/mL$ in B16-F1 melanocytes. The key gene and protein expression of tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced (-73% for TRP-1 protein at $200{mu}g/mL$ UMOE, p<0.05). MOE showed similar results to a slightly lesser degree. We found that myo-inositol, a major compound in lemon balm extracts, significantly reduced cellular melanin synthesis and its effect was greater than arbutin at 1 mM. These suggest that both MOE and UMOE have anti-melanogenic role by both direct inhibition of tyrosinase and down-regulation of gene expressions in melanogenesis. UV-irradiation slightly improved the anti-melanogenic activities. UMOE may be useful as natural anti-melanogenic biomaterials for functional foods and cosmetics.