Peripheral nerve injury (PNI), caused by contusions, fractures, and other traumas, may lead to abnormal sensory function, limited motor capabilities, neuropathic pain, and muscle atrophy, which can severely impact the patient’s quality of life. Post-PNI, Wallerian degeneration occurs, involving axonal degeneration and myelin sheath collapse. Notably, the dorsal root ganglia (DRG), as the primary sensory neurons in pain signal transmission, are crucial targets in neuropathic pain (NP) induced by PNI, and changes in these targets trigger a series of complex signaling pathway alterations. Among these, the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, as a vital regulator of cell survival and death, promotes Schwann cell proliferation and migration, thereby enhancing axonal growth and myelination to facilitate nerve regeneration, and supports the survival of DRG neurons to alleviate NP. Current treatment method, including stem cell transplantation and neurotrophic medications, all have certain limitations. Traditional Chinese medicine (TCM) has the advantages of low cost and few side effects, and is widely used for the treatment of PNI. This article reviews the relationship between oxidative stress, apoptosis, autophagy, inflammation, angiogenesis, the cell cycle, and other pathophysiological mechanisms in PNI and the PI3K/Akt signaling pathway, as well as its associated molecular targets. We also discuss the potential mechanisms of action of TCM monomers, compound formulas, and acupuncture based on the PI3K/Akt signaling pathway in the treatment of PNI, aiming to provide systematic and standardized theoretical guidance for the healing of PNI with TCM and a useful reference for the development of related medications.