Bone marrow mesenchymal stem cells (BMSCs) are non-hematopoietic multipotent stem cells capable of differentiating into mature cells. Isoquercetin, an extract from natural sources, has shown promise as a potential treatment for osteoporosis. To investigate the therapeutic effects of isoquercetin on osteoporosis, bone marrow mesenchymal stem cells (BMSCs) were cultured in vitro, and osteogenesis or adipogenesis was induced in the presence of isoquercetin for 14 days. We evaluated cell viability, osteogenic and adipogenic differentiation, as well as mRNA expression levels ofRunx2, Alpl, andOCNin osteoblasts, and mRNA expression levels ofPparγ,Fabp4, andCebpαin adipocytes. The results showed that isoquercetin dose-dependently increased cell viability and promoted osteogenic differentiation, as evidenced by Alizarin Red and alkaline phosphatase staining and mRNA expression levels ofRunx2,Alpl, andOCNin osteoblasts (P<0.05). In contrast, isoquercetin inhibited adipogenic differentiation and decreased the mRNA expression levels ofPparγ, Fabp4,andCebpαin adipocytes (P<0.05). In vivo, isoquercetin treatment increased bone quantity and density in an osteoporosis model mice group, as determined by μCT scanning and immunohistochemistry (P<0.05). These findings suggest that isoquercetin may have therapeutic potential for osteoporosis by promoting the proliferation and differentiation of BMSCs towards osteoblasts while inhibiting adipogenic differentiation.Graphical Abstract