The current study examined the protective benefits of Sida spinosa & Cissus Quadrangularis ethanolic fractions (SSEF & CQEF) in streptozotocin-induced diabetic nephropathy with the goal of developing complementary and alternative medicine for the treatment of diabetic nephropathy. Globally, diabetic nephropathy is now the most common cause of end-stage renal failure. Sida spinosa &Cissus Quadrangularis may halt the advancement of diabetic nephropathy because of their anti-inflammatory, anti-diabetic, and antioxidant properties. In this work, rats were given a single intraperitoneal injection of 45 mg/kg of streptozotocin (STZ) to cause diabetic nephropathy (DN). After 4 weeks, urine albumin was determined. Urine albumin more than 300 mg/24 hr confirmed the development of DN. For next eight weeks, oral dosages of SSEF & CQEF (200& 400 mg/kg) were administered to STZ-induced DN rats. Blood glucose levels, body & kidney weight were measured at the conclusion of the study after eight weeks. Parameters from serum like creatine, BUN, albumin, HbA1c and urine parameters like creatinine, 24 h urine output, albumin and creatinine clearance were examined. The kidney's antioxidant enzymes vs CAT, SOD & GSH were assessed and the kidney's histopathology was also examined. In the STZ-induced DN rats, SSEF & CQEF significantly increased body weight, decreased blood glucose levels, and lowered kidney weight at 400 mg/kg dose. Additionally, the fractions reduced the urine concentrations of albumin, blood urea nitrogen, and HbA1c. In the kidney, SSEF & CQEF markedly raised the antioxidant indices. A histological examination showed that the STZ induced DN rats treated with SSEF & CQEF had decreased tubule vacuolar degeneration& basement membranes thickening. Current research shows that SSEF & CQEF may have antioxidant, antihyperglycemic, and renoprotective properties that could be useful in reducing the progression of diabetic nephropathy.