Objective <p>Our meta-analysis aims to assess the efficacy of genetically modified stem cell therapy in preclinical osteoporosis models.</p> Methods <p>We executed a thorough literature search across PubMed, Embase, Web of Science, and the Cochrane Library databases from inception to September 15, 2023. We used a random-effect model for pooled analysis of the effect of genetically modified stem cell therapy on animals with osteoporosis. The primary outcomes included bone mineral density (BMD) and bone volume fraction.</p> <p>(BV/TV). All meta-analyses were performed employing the Cochrane Collaboration's Review Manager (version 5.3) in conjunction with Stata 15.0 statistical software.</p> Results <p>A total of 2567 articles were reviewed, of which 16 articles met inclusion criteria. Of these, 13 studies evaluated the BMD and 11 studies evaluated BV/TV. Compared to the control group, genetically modified stem cell therapy was associated with significantly improved BMD (standardized mean difference [SMD] = 1.85, 95% Confidence Interval [CI]: 1.06–2.63, <i>P</i> &lt; 0.001, I² = 69%) and BV/TV (standardized mean difference [SMD] = 2.11, 95% Confidence Interval [CI]: 1.10–3.12, <i>P</i> &lt; 0.001, I² = 78%).</p> Conclusion <p>Genetically modified stem cell therapy is a safe and effective method that can significantly improve the BMD and BV/TV in animal models of osteoporosis. These results provide an important basis for future translational clinical studies of genetically modified stem cells.</p>