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Diabetic peripheral neuropathy(DPN) is a common complication of diabetes, characterized by a complex pathogenesis for which no specific mechanism has yet been clearly identified. Studies have shown that the onset and progression of DPN are mainly associated with inflammation, oxidative stress, autophagy dysfunction, lipid metabolism disorders, iron metabolism disturbances, and vascular lesions. Clinically, commonly used therapeutic agents primarily focus on nourishing nerves and improving microcirculation, including mecobalamin, gangliosides, inositol, and ginkgolide glycosides. However, no curative treatment is currently available, and drug therapies generally show unsatisfactory efficacy. According to traditional Chinese medicine(TCM), DPN falls under the categories of "blood impediment" and "impediment syndrome", and is considered to result from the failure of the sinews and vessels to receive proper nourishment, leading to numbness in the limbs. The underlying pathogenesis is attributed to Qi deficiency and blood stasis. Therefore, TCM offers distinct advantages in the treatment of DPN and has achieved favorable therapeutic outcomes. TCM therapies are characterized by multi-target, multi-pathway mechanisms and low incidence of side effects, making them suitable for managing chronic diseases such as DPN. Huangqi Guizhi Wuwu Decoction, recorded in the Synopsis of the Golden Chamber(Jin Gui Yao Lue), is a representative classical prescription for treating blood impediment. It functions to regulate and tonify Qi and blood and to warm and unblock the meridians and collaterals, which aligns well with the fundamental TCM pathogenesis of Qi stagnation and blood stasis in DPN. Recent research has shown that Huangqi Guizhi Wuwu Decoction can exert therapeutic effects on DPN through pathways including antioxidative stress, anti-inflammatory responses, inhibition of cell apoptosis, and improvement of microcirculation. These effects have been validated not only in cell and animal studies but also in clinical trials, confirming its definite therapeutic efficacy for DPN. This study elucidates the pathogenesis of DPN from both TCM and modern biomedical perspectives, discusses the specific pathways and mechanisms by which Huangqi Guizhi Wuwu Decoction acts in the context of DPN, and elaborates on its mechanisms at both molecular and formula levels. This study is expected to provide a theoretical and practical reference for future TCM-based prevention and treatment strategies for DPN, as well as for the development of novel therapeutic agents.