Autogenous fat grafting (AFG) and platelet-rich plasma (PRP) have emerged as promising regenerative therapies in peripheral nerve repair, particularly in the context of sciatic nerve injuries. The sciatic nerve, being the largest peripheral nerve in the body, is critical for motor and sensory function, and its regeneration remains a significant clinical challenge. This review article comprehensively examines the current evidence on the use of AFG and PRP in sciatic nerve graft regeneration, focusing on their mechanisms of action, efficacy, and potential synergies. AFG provides a scaffold rich in adipose-derived stem cells (ASCs) and growth factors, promoting angiogenesis, reducing fibrosis, and enhancing axonal regrowth. PRP, on the other hand, delivers a concentrated pool of growth factors and cytokines that modulate inflammation, stimulate cellular proliferation, and support tissue remodeling. Preclinical and clinical studies suggest that both AFG and PRP can significantly improve nerve regeneration outcomes, including functional recovery and histological evidence of axonal regrowth. Furthermore, combining these therapies may offer additive or synergistic benefits, enhancing the regenerative microenvironment. However, challenges such as standardization of protocols, optimal timing of application, and long-term outcomes remain to be addressed. This review highlights the potential of AFG and PRP as adjuncts to traditional nerve grafting techniques, offering new avenues for improving functional recovery in patients with sciatic nerve injuries.