BACKGROUND Sida cordifolia and Sida rhombifolia are regarded as useful herbs as they have been shown to be effective, inexpensive and harmless in the prevention of diabetes, and are recognized as valuable therapeutic substances. OBJECTIVE The purpose of this study was to assess the effect of S. cordifolia and S. rhombifolia in the treatment of diabetic nephropathy using a rat model. METHODS Extracts of S. cordifolia and S. rhombifolia were obtained using the Soxhlet method. The hydroalcoholic extract solvent was used in the following proportions: 70:30, 50:50 and 80:20. The 80:20 hydroalcoholic extract was observed to be the most potent. The inhibitory effects of the extract were determined using the α-amylase assay. The most potent extract also underwent total flavonoid, phenolic and free radical scavenging tests, and was incorporated into an animal study. Diabetes was induced in rats by administering nicotinamide (NAD; 230 mg/kg) and streptozotocin (STZ; 65 mg/kg) intraperitoneally. In addition to a standard control of pioglitazone, the rats received extract dosages of 100 mg/kg/day or 200 mg/kg/day. Body weight, blood glucose, glycated hemoglobin (HbA1c), blood urea nitrogen (BUN), serum albumin, serum creatinine, homeostatic model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance were assessed at various time points. The animals also underwent histopathological examination to observe alterations induced by the treatment. RESULTS Sida cordifolia was the most successful in lowering blood glucose and HbA1c levels. Renal function indices and antioxidant enzyme levels were regained in a dose-dependent manner. Furthermore, S. cordifolia (200 mg/kg/day) extract, similar to pioglitazone, inhibited the production of advanced glycation byproducts by the kidney. CONCLUSIONS The effects of various S. cordifolia and S. rhombifolia extracts on rats with diabetic nephropathy were observed. Sida cordifolia may be further explored for the treatment of diabetic nephropathy and, due to its diverse nature, may be utilized for the treatment of a wide range of diseases, as it provided more significant findings.