Stroke occurs when the blood flow to the brain is interrupted due to a rupture of blood vessels or blockage in the brain. It is the major cause of physical disabilities in adulthood. Despite advances in surgical and pharmacological therapy, functional recovery from stroke is limited, affecting quality of life. Stem cell therapy, which may treat neurological disorders associated with brain traumas, including stroke, is an important focus in stroke research and treatment. Stem cell therapy has primarily used a type of adult stem cells called mesenchymal stem cells (MSCs) due to their universality and ability to develop into multiple lineages to regenerate brain cells and repair brain tissues. A significant number of clinical studies provide evidence of the potential of MSCs to treat stroke. This review summarizes the therapeutic mechanism and applications of MSCs in stroke treatment. We also highlight the current challenges and future prospects of adult MSC therapy for stroke treatment.