Steadily rising population ageing is a global demographic trend due to the advancement of new treatments and technologies in the medical field. This trend also indicates an increasing prevalence of age-associated diseases, such as loss of muscle mass (sarcopenia), which tends to afflict the older population. The deterioration in muscle function can cause severe disability and seriously affects a patient’s quality of life. Currently, there is no treatment to prevent and reverse age-related skeletal muscle ageing frailty. Existing interventions mainly slow down and control the signs and symptoms. Mesenchymal stem cell-derived extracellular vesicle (MSC-EV) therapy is a promising approach to attenuate age-related skeletal muscle ageing frailty. However, more studies, especially large-scale randomised clinical trials need to be done in order to determine the adequacy of MSC-EV therapy in treating age-related skeletal muscle ageing frailty. This review compiles the present knowledge of the causes and changes regarding skeletal muscle ageing frailty and the potential of MSC-EV transplantation as a regenerative therapy for age-related skeletal muscle ageing frailty and its clinical trials.