Diabetic kidney disease (DKD) serves as the leading factor in the development of chronic kidney disease, which Progress to end-stage renal failure. Metformin is the first-line therapy indicated for diabetes but it has many side effects including gastrointestinal tract (GIT) disturbance. Researchers have developed various antidiabetic drugs that can reveal hypoglycemia, such as dipeptidyl peptidase 4 (DDP-4) inhibitors such as vildagliptin. This study shows the therapeutic value of metformin and vildagliptin in rat models of STZ-induced DKD.  Diabetes was produced in the experimental rats by feeding on a high-fat-high fructose diet (HFHF) and intraperitoneal (I.P) injection of single low-dosage streptozotocin (35 mg/kg.BW). As soon as the development of diabetes, metformin (100 mg/kg/day) and vildagliptin (6 mg/kg/day) were administered orally for eight weeks. The biochemical parameters of blood glucose, serum insulin, creatinine, urea, serum albumin, and lipid profile were evaluated. The levels of serum oxidant/ antioxidant markers Malondialdehyde (MDA) and total antioxidant capacity (TAC) were determined. Treatment with metformin and vildagliptin dramatically improved The biochemical parameters of serum glucose, insulin, urea, creatinine, serum albumin, lipid profile, and oxidative stress via oxidant/antioxidant activity (MDA and TAC) showed that vildagliptin outperformed metformin in almost all of the assayed parameters.