Nuclear accidents and terrorism present a serious threat for mass casualty. Accidental or intended radiation exposure leads to radiation-induced gastrointestinal (GI) syndrome. However, currently there are no approved medical countermeasures for GI syndrome. Thus, developing novel treatments for GI syndrome is urgent. Mesenchymal stem cells (MSCs) derived from bone marrow are a subset of multipotent adult somatic stem cells that have the ability to undergo self-renewal, proliferation and pluripotent differentiation. MSCs have advantages over other stem cells; they can be easily isolated from patients or donors, readily expanded ex vivo, and they possess reparative and immunomodulatory properties. Moreover, MSCs have been shown to be powerful tools in gene therapy and can be effectively transduced with vectors containing therapeutic genes. Therefore, the therapeutic potential of MSCs has been brought into the spotlight for the clinical treatment of GI syndrome. In this review, we discuss the possible role of MSCs in radiation-induced GI syndrome.