Objective The purpose of this study was to determine the effect of tripterygium glycosides (TGs) on regulating abnormal lipid deposition in nephrotic syndrome (NS) rats. Methods Sprague-Dawley (SD) rats were injected with 6 mg/kg doxorubicin to construct nephrotic syndrome models (n = 6 per group), and then administered with TGs (10 mg/kg center dot d(-1)), prednisone (6.3 mg/kg center dot d(-1)), or pure water for 5 weeks. Biomedical indexes, such as urine protein/creatinine ratio (PCR), blood urea nitrogen (BUN), serum creatinine (Scr), serum albumin (SA), triglycerides (TG), total cholesterol (TC)were investigated to evaluate the renal injury of rats. H&E staining experiment was used to assess the pathological alterations. Oil Red O staining was used to assess the level of renal lipid deposition. Malondialdehyde (MDA) and glutathione (GSH) were measured to assess the extent of oxidative damage to the kidney. TUNEL staining was used to assess the status of apoptosis in the kidney. Western blot analysis was performed to examine the levels of relevant intracellular signaling molecules. Results After treatment with TGs, those tested biomedical indexes were significantly improved, and the extent of kidney tissue pathological changes and lipid deposition in the kidney was diminished. Treatment with TGs decreased renal oxidative damage and apoptosis. Regarding the molecular mechanism, TGs significantly increased the protein expression levels of Bcl-2 but decreased the levels of CD36, ADFP, Bax, and Cleaved caspase-3. Conclusion TGs alleviates renal injury and lipid deposition induced by doxorubicin, suggesting that it may be a new strategy for reducing renal lipotoxicity in NS.