Objective <p>To systematically review the effect of applying mesenchymal stem cells (MSCs) and gene-therapy approach on the bone formation of the distracted area in the maxillofacial region.</p> Study Design <p>Studies that delivered genetically modified or unmodified MSCs or used gene-therapy methods without MSCs delivery for the mandibular or maxillary distraction osteogenesis (DO) treatment in both human and animal models were included.</p> Results <p>From a total of 720, 32 animal studies and one human study were included. Results of human study showed that the injection of bone marrow MSCs has no significant complications and can induce significant bone formation. Results of animal studies showed that applying of MSCs as the study group results in higher values of bone formation variables, namely new bone formation and volume, bone volume/total tissue volume, bone mineral density and thickness of the new trabeculae compared to control group. Meta-analysis revealed that in rabbit models, significant increase was observed in the bone formation percentage after MSCs injection. In the goat models, stem cell injection showed significant increase in trabecular thickness.</p> Conclusion <p>In animal models, the use of MSCs in distraction osteogenesis (DO) treatment of the maxillofacial region did not result in significant complications and showed potential positive outcomes on bone formation. However, more clinical and animal studies with a lower risk of bias are required to fully establish the efficacy and safety of this approach.</p>