The pathogenesis of diabetic nephropathy is complex and can ultimately progress to end-stage renal disease, imposing a heavy burden on patients. Current treatment methods show limited efficacy. The protein kinase RNA-like endoplasmic reticulum kinase(PERK)-eukaryotic initiation factor-2α (eIF2α)-activating transcription factor 4 (ATF4) -C/EBP homologous protein (CHOP) signaling pathway serves as a critical pathway in endoplasmic reticulum stress, with downstream regulation of pathological processes such as apoptosis and autophagy closely related to the progression of diabetic nephropathy. Traditional Chinese medicine regulates the PERK-eIF2α-ATF4-CHOP pathway through methods that tonify Qi and nourish Yin, strengthen the spleen and benefit the kidneys, promote diuresis and reduce edema, clear heat and detoxify, as well as invigorate blood and eliminate stasis. These interventions protect the glomerular filtration barrier, reduce capillary basement membrane thickening, enhance protein reabsorption in urine, and delay renal interstitial fibrosis. The mechanistic role of the PERK-eIF2α-ATF4-CHOP signaling pathway in diabetic nephropathy was elucidated, the theoretical basis for traditional Chinese medicine interventions in this pathway was summarized, and recent advances were reviewed in the mechanisms of action of effective components of traditional Chinese medicine targeting this pathway, aiming to provide new ideas and methods for the prevention and treatment of diabetic nephropathy through traditional Chinese medicine.