Long-term alcohol abuse causes musculoskeletal disorders, among of which, alcohol-induced osteonecrosis of the femoral head (ONFH) is of concern due to its significant and severe complications. A variety of methods have been attempted to prevent alcohol-induced ONFH, and monomers extracted from Chinese herbs might benefit the disease profoundly. In the current study, muscone, the main ingredient of musk, was used to prevent alcohol-induced ONFH. In vitro, ethanol was used to affect the potential of osteogenesis and proliferation of human bone mesenchymal stem cells (hBMSCs), and beneficial role of muscone was investigated on hBMSCs. In vivo, following the establishment of alcohol-induced ONFH, muscone was employed to treat the diseased rats, which were analyzed by micro-CT scanning and a series of histologic staining. As a result, we found ethanol could significantly suppress osteogenic differentiation of hBMSCs, while muscone held the potential to promote ALP activity and mRNA expressions of COL1 and OCN under ethanol treatment. Meanwhile, imaging analysis revealed muscone could restore BV/TV ratio and bone mineral density of the necrotic femoral head, and the protective role of muscone on alcohol-induced ONFH was further confirmed by histologic examinations. Our study confirmed the protective effect of muscone against alcohol-induced ONFH both in vitro and in vivo. Therefore, muscone may be considered as a valuable therapeutic natural drug for alcohol-induced ONFH in humans.