The concern to identify a more benign alternative for whitening agents is gaining significant attention in recent investigations. Therefore, this study aimed to investigate the ability of laccase isolated from Trametes polyzona to degrade melanin and explore potential natural phenolic mediators enhancing degradation process. Among phenolic mediators tested, gallic acid showed the most potential for melanin degradation due to 3-fold enhancement, with the highest rate of 77.8 % during a 24-h reaction. The addition of sodium azide inhibited melanin degradation to approximately 56 %, showing the significant role of laccase. The results of Scanning Electron Microscope analysis after treatment showed that the morphology of melanin was significantly altered, with rough and porous surface, as well as small uniform size. However, the untreated melanin had a smooth surface, a round shape, and a larger size. In vitro and molecular docking analyses mutually supported the occurrence of the laccase mediator system in melanin degradation.