AbstractMesenchymal stem cells (MSCs) have been extensively studied and implicated for the cell-based therapy in several diseases due to theirs immunomodulatory properties. Embryonic stem cells and induced-pluripotent stem cells have either ethical issues or concerns regarding the formation of teratomas, introduction of mutations into genome during prolonged culture, respectively which limit their uses in clinical settings. On the other hand, MSCs also encounter certain limitation of circumscribed survival and reduced immunomodulatory potential during transplantation. Plethora of research is undergoing to improve the efficacy of MSCs during therapy. Several compounds and novel techniques have been employed to increase the therapeutic potency of MSCs. MSCs secreted superoxide dismutase 3 (SOD3) may be the mechanism for exhibiting direct antioxidant activities by MSCs. SOD3 is a well known antioxidant enzyme and recently known to possess immunomodulatory properties. Along with superoxide scavenging property, SOD3 also displays anti-angiogenic, anti-chemotactic and anti-inflammatory functions in both enzymatic and non-enzymatic manners. In this review, we summarize the emerging role of SOD3 secreted from MSCs and SOD3’s effects during cell-based therapy.