Myeloma bone disease (MBD) is one of the most common complications of multiple myeloma (MM). MBD is considered to be caused by the activation of osteoclasts and suppression of osteoblasts resulting from the involvement of neoplastic plasma cells and the change of bone marrow microenvironment. It may be a feasible way to improve the treatment of MBD by promoting osteogenic differentiation of bone marrow mesenchymal stem cell (BMSC), from which the osteoblasts mainly originate. Resveratrol (RES), a naturally occurring polyphenolic flavonoid compound, was reported to function in the modulation of bone metabolism. But the effects of RES on osteogenic differentiation of MM derived BMSC (MM-BMSC) and its underlying mechanism remains unknown. Totally 10 cases of MM-BMSCs were isolated, cultured and identified successfully in the present study. RES was found to promote osteogenic differentiation of MM-BMSC by alkaline phosphatase activity assay, qRT-PCR and alizarin red staining. SIRT1 was predicted to be the target gene of RES in promoting osteogenic differentiation with bioinformatic analysis. RES upregulated the expression of silent information regulator 1 (SIRT1) in MM-BMSC (P<0. 001) and its osteogenic differentiation was inhibited in the SIRT1 small interfering RNA (si-SIRT1) transfected group. Furthermore, the mRNA (P<0. 001) and protein (P<0. 01) expression of runt related transcription factor 2 (RUNX2) was increased in the RES treated group and decreased (mRNA P < 0. 01, protein P < 0. 05) in si-SIRT1 transfected group, respectively. In conclusion, resveratrol promotes osteogenic differentiation of MM-BMSCs via upregulating SIRT1/RUNX2 and seems to be a potential therapeutic agent to counteract bone disease in MM patients.