BACKGROUND: This meta-analysis aimed to pool the existing evidence to determine the clinical efficacy and safety of mesenchymal stem cells (MSC) in patients with non-unions. METHODS: A systematic search in PubMed and Scopus was performed until October 2024 to gather pertinent studies. The inclusion criteria included participants with non-unions, the intervention of MSC administration, a comparator of standard treatment (bone graft), and outcomes focused on healing rate, healing time, or side effects. The Jadad score Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias in randomized and non-randomized studies, respectively. Moreover, GRADE criteria were used to assess the quality of evidence. Using a random effects model, odds ratios (OR) with 95% confidence intervals (CIs) were calculated for healing and complication rates, while standardized mean differences (SMD) with their 95% CIs were used to assess the impact of MSC therapy on bone union time. RESULTS: Twenty-one studies, with 866 patients, were included. The bone healing rates were 44% at 3 months, 73% at 6 months, 90% at 9 months, and 86% at 12 months, eventually reaching 91% after 12 months of follow-up. MSC therapy, with or without scaffolds, was linked to higher odds of bone healing rate at 3 and 6 months, compared to bone grafts as the standard care (OR = 1.69). The time to union following the treatment was 6.30 months (95%CI: 86-96%), with patients treated with MSC/Scaffold experiencing a shorter time compared to MSC alone (5.85 vs. 6.36 months). MSC therapy significantly decreased bone union time (SMD:-0.54 months, 95% CI: -0.75 to -0.33). The complication rate was 1% (MSC/Scaffold: 0%, MSC alone: 2%), with MSC alone or MSC/Scaffold showing a lower risk than the standard care (OR = 0.41, 95% CI: 0.22-0.78). CONCLUSION: MSC is a potential adjunct therapy for patients with non-union fractures. CLINICAL TRIAL NUMBER: Not applicable.