Abstract: Sciatic nerve injury is a severe insult to the nervous system that causes persisting neurological deficits, and is a type of peripheral neuropathy that can lead to persistent neurological dysfunction. The currently available treatments involve surgery, medications, and rehabilitative traction. However, none of these techniques can markedly reverse neurological deficits. Recently, extracellular vesicles from various cell sources have been applied to different models of sciatic nerve injury, thereby generating new cell-free therapies for the treatment of sciatic nerve injury. However, the use of extracellular vesicles alone is still associated with some notable shortcomings, such as, the size of human muscle tissue is large, the sciatic nerve is the largest nerve in the body, severe sciatic nerve injury is often large and complex, and it is unknown whether extracellular vesicles can achieve the same therapeutic effect in muscle tissue. Therefore, this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for sciatic nerve injury, including the combination of extracellular vesicles and biomaterials, drugs and external stimuli, which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles. In addition, this paper also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of sciatic nerve injury.