Zingerone, 4‐(4‐hydroxy‐3‐methoxyphenyl)‐2‐butanone (Zg), a phenolic compound isolated from ginger is reported to have anti‐inflammatory and antidiabetic properties. However, its role in the promotion of osteogenesis is not known. In this study, we investigated the therapeutic effect of Zg on osteogenesis at the cellular and molecular levels. Zg treatment was nontoxic to mouse mesenchymal stem cells (mMSCs). At the cellular level, it enhanced osteoblast differentiation as evidenced by more calcium deposits. At the molecular level, Zg stimulated the expression of Runx2 (a bone transcription factor) and other marker genes of osteoblast differentiation in mMSCs. Recent studies indicated that microRNAs (miRNAs) regulate bone metabolism, and we identified that Zg treatment in mMSCs upregulated mir‐590, a positive regulator of Runx2 by targeting Smad7, an antagonist of TGF‐β1 signaling. Thus, the osteogenic potential of Zg would be beneficial for treating bone and bone‐related diseases.