Melanin provides inherent protection against skin cancer by absorbing broad-spectrum radiant energy of UV radiation. Cutaneous malignant melanoma incidence has recently been observed to increase and the frequency is closely associated with the skin color, highlighting the importance of skin pigmentation. Here, we showed how melanin biosynthesis is enhanced by treatment with phenolic compounds-rich Cymbopogon schoenanthus (CYM) in B16 murine melanoma cells and human epidermal melanocytes (HEM). CYM increased the melanin content of the cells by upregulating the expression of tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase (DCT) at the protein and mRNA levels, comparable to the effect of α-melanocyte-stimulating hormone (MSH), in both B16 cells and HEM. Moreover, global gene expression analysis showed that at least 44 pigmentation-associated genes were modulated, including the microphthalmia-associated transcription factor (Mitf) and its transcriptional regulators (Sox10, Pax3, and Lef1). Upregulation of copper transport-associated gene Atp7b indicates that CYM also promotes tyrosinase activity. CYM upregulated Mitf and possibly activates tyrosinase enzyme, providing evidence for its possible use to promote melanogenesis and as a therapeutic agent against hypopigmentation disorders.