(2′R)‐2′,3′‐Dihydro‐2′‐(1‐hydroxy‐1‐methylethyl)‐2,6′‐bibenzofuran‐6,4′‐diol (DHMB) is a natural compound extracted from Morus notabilis. It was found that DHMB acts as a competitive inhibitor against mushroom tyrosinase with a Ki value of 14.77 μM. Docking results further indicated that it could form strong interactions with one copper ion with a distance of 2.7 Å, suggesting the mechanism of inhibition might be due to chelating copper ions in the active site. Furthermore, melanin production in B16‐F10 murine melanoma cells was significantly inhibited by DHMB in a concentration‐dependent manner without cytotoxicity. The results of western blotting also showed that DHMB decreased 3‐isobuty‐1‐methxlzanthine‐induced mature tyrosinase expression. Taken together, these findings indicated that DHMB may be a new promising pigmentation‐altering agent for agriculture, cosmetic, and therapeutic applications. Copyright © 2015 John Wiley & Sons, Ltd.