This study investigates the intervention effects and mechanisms of astragaloside IV (AS-IV) on diabetic nephropathy (DN) mice based on network pharmacology and experimental validation. A DN mouse model was established using a high-fat diet combined with low-dose streptozotocin. Mice received continuous intervention with different doses of AS-IV for 12 weeks. Renal protective effects of AS-IV were evaluated by measuring fasting blood glucose, renal function indicators, renal histopathology, and markers of oxidative stress and inflammatory response. Network pharmacology screening identified common targetsbetween AS-IV and DN, followed by GO and KEGG enrichment analyses to select key signaling pathways. Molecular docking of key targets was performed using AutoDock Vina software and validated via Western blot. Results demonstrated that AS-IV significantly reduced fasting blood glucose levels in DN mice,improved renal function, and mitigated renal histopathological damage. It decreased levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and malondialdehyde (MDA), increasedsuperoxide dismutase (SOD) and reduced glutathione (GSH) activity, and suppressed renal tissue alpha-smooth muscle actin (α-SMA) expression. Network pharmacology analysis indicates that AS-IV primarily actsonkey targets including AKT serine/threonine kinase 1（AKT1）, mechanistic target of rapamycin（mTOR）, tumor necrosis factor（TNF）and cysteine-aspartic acid protease 3（Caspase-3）, with significant enrichment in the phosphatidylinositol 3-kinase/protein kinase B/mTOR (PI3K/AKT/mTOR) signaling pathway.Molecular docking analysis revealed strong binding affinity between AS-IV and PI3K, AKT and mTOR. Western blot analysis further confirmed that AS-IV significantly suppressed the expression levels of PI3K, p-AKT and p-mTOR proteins in renal tissues of DN mice. In summary, AS-IV may exert renal protective effects by blocking the abnormal activation of the PI3K/AKT/mTOR signaling pathway, thereby alleviating oxidative stress and inflammatory responses, improving renal function, and delaying the progression of renal fibrosis.