Abstract: Diabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes mellitus. Therapies aimed at strengthening the spleen and benefiting the kidney have shown notable efficacy in the treatment of DKD, including reducing proteinuria, delaying the decline in renal function, improving glucolipid metabolic disorders, and alleviating micro-inflammation and oxidative stress. Regarding the relevant mechanisms of action, numerous studies have demonstrated that formulas focused on strengthening the spleen and benefiting the kidney achieve therapeutic effects on DKD through multiple pathological mechanisms, including regulating glucolipid metabolism, inhibiting inflammatory responses and oxidative stress, protecting podocytes, modulating programmed cell death, and inhibiting renal fibrosis. This review systematically summarizes the clinical application of strengthening spleen and benefiting kidney therapy in the treatment of DKD, as well as the multi-pathway biological regulatory mechanisms involved, based on a comprehensive review of discussions of DKD in classical Chinese medical literature and the clinical experience of renowned modern practitioners. However, current research still has limitations, including a lack of high-quality real-world epidemiological investigations of traditional Chinese medicine (TCM) patterns, insufficient clinical evidence, and inadequate systematic mechanistic studies. Future research should follow the progressive logic of “confirmation of pathogenesis-validation of therapeutic efficacy-elucidation of mechanisms”. First, epidemiological investigations of the distribution of TCM patterns in DKD should be conducted to establish real-world evidence for the core pathogenesis. Then, high-quality clinical efficacy evaluation studies should be conducted. Finally, multiomics and systems biology approaches should be integrated to elucidate the pharmacodynamic material basis and scientific connotation of representative formulas, thereby promoting the optimization of clinical treatment strategies and the development of novel therapeutics for TCM treatment of DKD.