Peripheral nerve injury (PNI) is a common disease that is difficult to nerve regeneration with current therapies. Fortunately, Zou et al demonstrated the role and mechanism of bone marrow derived mesenchymal stem cells (BMSCs) in promoting nerve regeneration, revealing broad prospects for BMSCs transplantation in alleviating PNI. We confirmed the fact that BMSCs significantly alleviate PNI, but there are shortcomings such as low cell survival rate and immune rejection, which limit the wide application of BMSCs. BMSCs-derived exosomes (Exos) are considered as a promising cell-free nanomedicine for PNI, avoiding the ethical issues of BMSCs. Exos in combination with bioengineering therapeutics (including extracellular matrix, hydrogel) brings new hope for PNI, provides a favorable microenvironment for neurological restoration and a therapeutic strategy with a favorable safety profile, significantly increases expression of neurotrophic factors, promotes axonal and myelin regeneration, and demonstrates a strong potential to enhance neurogenesis. Therefore, engineered Exos exhibit better properties, such as stronger targeting and more beneficial components. This article briefly describes the role of nanotechnology and bioengineering therapies for BMSCs in PNI, proposes clinical application prospects and challenges of nanotechnology and bioengineering BMSCs-derived Exos in PNI to improve the efficacy of BMSCs in the treatment of PNI.