Bone marrow mesenchymal stem cell transplantation (BMSCT) is a potential treatment for osteoporosis, capable of contributing to bone tissue repair. BMSCT has demonstrated osteoinductive effects and the ability to regulate microenvironmental metabolism; however, its role and mechanisms in bone loss due to reduced estrogen levels remain unclear. In this study, the effect of BMSCT on ovariectomy (OVX)-induced osteoporosis in mice was assessed, and liquid chromatography-mass spectrometry (LC-MS) metabolomic studies of bone tissue were conducted to identify potential metabolic molecular markers. The results revealed that BMSCT reduces OVX-induced bone loss in mice while improving the mechanical properties of mouse femurs and increasing the expression of osteogenic markers in peripheral blood. In a metabolomic study, 18 metabolites were screened as potential biomarkers of the anti-osteoporotic effect of BMSCT. These metabolites are mainly involved in arachidonic acid metabolism, taurine and hypotaurine metabolism, and pentose and glucuronate interconversions. Collectively, these results illustrate the correlation between metabolites and the underlying mechanisms of osteoporosis development and are important for understanding the role and mechanisms of exogenous bone marrow mesenchymal stem cells (BMSCs) in osteoporosis management. This study lays the foundation for research on BMSCs as a treatment strategy for osteoporosis.