Diabetic nephropathy (DN) is considered a clinical syndrome, which is a diabetic kidney disease characterized by increasing blood pressure, albuminuria, and chronic kidney disease. The current study aimed to determine the effect of sweetener (Stevia rebaudiana) on diabetic nephropathy in a diabetic rat model. Four groups (n = 7) of male albino rats (Rattus norvegicus): the control group (healthy); the other three groups were diabetic (induced streptozotocin intraperitoneally), one as non-treated and two diabetic rat groups treated with 2 doses of stevia (200 and 400 mg/kg body weight, respectively) daily for 4 weeks. Biomarkers of nephropathy were measured in plasma and kidneys at the end of the experiment. The levels of plasma glucose, urea, uric acid, creatinine, renal malondialdehyde (MDA), and caspase-3 significantly increased in diabetic rats and levels of insulin, renal catalase, superoxide dismutase, and vascular endothelial growth factor A (VEGF-A) were significantly decreased compared to the healthy control group. After treating the diabetic rats with natural sweetener (stevia), the kidney and plasma biochemical parameters were improved significantly. These results indicated the major role of stevia in controlling diabetic nephropathy.