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Peripheral nerve injuries remain a common clinical complication, and currently available therapies present significant limitations, often resulting in poor and suboptimal outcomes. Despite significant developments in microsurgical approaches in the last decades, no effective treatment options have been disclosed. Current research focuses on the optimization of such microsurgical techniques and on their combination with other pro-regenerative factors, such as mesenchymal stem cells or biomaterials. Mesenchymal stem cells present a remarkable capacity for bioactive molecule production that modulates inflammatory and regenerative processes, stimulating peripheral nerve regeneration. In parallel, efforts have been directed towards the development of biomaterial nerve guidance channels and nerve conduits. These biomaterials have been optimized in terms of biodegradability, ability to release bioactive factors, incorporation of cellular agents, and internal matrix architecture (to enable cellular migration and mimic native tissue morphology and to generate and bear specific electrical activity). The current literature review presents relevant advances in the development of mesenchymal stem cell and biomaterial-based therapeutic approaches aiming at the peripheral nerve tissue regeneration in diverse lesion scenarios, also exploring the advances achieved by our research group in this field in recent years.