Abstract: Central nervous system diseases such as stroke, traumatic brain injury (TBI), and white matter disease (WMD) are mainly involved in the loss of function caused by neuronal apoptosis and lack of effective treatment. Mesenchymal stem cell (MSC) is a heterogeneous stem cell population with strong potential of tissue repair and immunomodulation. It has many sources and is considered to be less immunogenic. Most preclinical studies on central nervous system diseases by transplantation of MSC have achieved good safety and efficacy results, and clinical trials based on MSC transplantation are under way. However, issues concerning the identification of MSCs, the optimal route of transplantation, the long-term efficacy and safety of treatment as well as immunogenicity are still controversial. This article reviews the research progress of MSC in the treatment of stroke, TBI and WMD from the aspects of effectiveness and safety.