Background <p>Age-related bone loss is closely associated with functional decline and exhaustion of bone marrow mesenchymal stem cells (BMSCs). This study aimed to investigate whether combined Metformin and Taurine (Met + Ta) treatment could attenuate aging-associated skeletal deterioration and preserve BMSC function.</p> Methods <p>Eighteen-month-old male C57BL/6J mice were treated with Met, Ta, or Met + Ta for 8 consecutive weeks. Bone microarchitecture was evaluated by micro-computed tomography and histological staining. BMSCs were isolated from aged mice and assessed for osteogenic differentiation, proliferative capacity, senescence-related changes, and inflammatory cytokine production. Transcriptomic analysis was performed to identify molecular changes associated with Met + Ta treatment, and siRNA-mediated <i>Crebrf</i> knockdown was used for functional validation.</p> Results <p>Met + Ta treatment improved bone mass and trabecular microarchitecture more effectively than either single treatment. Histological staining further showed better preservation of trabecular structure and increased collagen-rich matrix deposition in the Met + Ta group. BMSCs from Met + Ta-treated mice exhibited enhanced osteogenic differentiation, increased proliferative activity, reduced senescence-associated phenotypes, and improved inflammatory homeostasis. Transcriptomic analysis revealed coordinated regulation of genes involved in proliferation, senescence, metabolism, proteostasis, and genome maintenance. Crebrf was identified as a candidate regulatory mediator, and <i>Crebrf</i> knockdown attenuated the anti-senescent and cellular-stability-related effects of Met + Ta in BMSCs.</p> Conclusions <p>Combined Met and Ta treatment alleviates age-related bone loss and preserves BMSC function more effectively than single-agent treatment. These findings suggest that Met + Ta may represent a potential combined strategy for delaying skeletal aging, with <i>Crebrf</i> serving as a candidate mediator of its protective effects.</p>