Peripheral nerve injury results in severe loss of motor and sensory function in the affected limb. The gold standard for peripheral nerve repair is autologous nerve grafts, but their inherent drawbacks limit their use. Satisfactory clinical data are yet to be obtained using tissue engineered nerve grafts with neurotrophic factors introduced in these grafts for nerve repair. Therefore, peripheral nerve regeneration still remains a challenge for clinicians. Exosomes are secreted nanovesicles from the extracellular membrane. They are critical for communication within the cell and play a crucial role in the pathologic process of the peripheral nervous system. Recent research supports the role of exosomes in exhibiting neurotherapeutic effects through axonal growth, Schwann cell activation, and regulating inflammation. Indeed, the use of “smart” exosomes by reprogramming or manipulating the secretome contents and functions are rising as a therapeutic option for treating peripheral nerve defects. This review provides an overview on the promising role of exosomes in the process of peripheral nerve regeneration.