Abstract: Currently, hormonal drugs are the first choice for the treatment of acute graft-versus-host disease (aGVHD). The second-line treatment drugs for aGVHD include basiliximab, methotrexate (MTX), ruxolitinib, etc. Antithymocyte globulin (ATG), mesenchymal stem cells (MSCs), and fecal bacterial transplantation are also used in the treatment of GVHD. In recent years, MSCs employed for the prevention and treatment of GVHD after allo-HSCT have generated a wealth of basic and clinical research. MSCs can achieve immunosuppressive function through cell-to-cell contact and release of immunomodulatory factors. Soluble factors, oxygen concentration, distinct ligands of Toll-like receptors (TLR), injection dose, immunosuppressant adoption and temperature control are engaged in the therapeutic effects of MSCs, yet their underlying mechanisms remain to be elucidated. Most studies have revealed that MSCs therapy could benefit acute and chronic GVHD, but that still remains to be confirmed due to lack of large-scale randomized controlled trial. This paper summarizes the main treatment methods for GVHD, with focus on the clinical research and mechanism of the cutting-edge technology of MSCs, and attempts to provide some insight for further development of new therapeutic strategies.