The present study was designed to investigate the effect of methanolic extract of Costus pictus (MECP) per se and in combination with drugs (Metformin and Enalapril) used in clinical practice in streptozotocin (STZ) induced diabetic nephropathy (DN) in rats. Diabetes was induced in male Wistar rats by a single injection of STZ (50mg/kg i.p.). After 28 days diabetic rats were divided into six groups. Two groups were treated with MECP (200mg/kg p.o.), MECP (400mg/kg p.o.) respectively; one group was treated with metformin (225mg/kg), enalapril (3.2mg/kg) combination; and two groups were treated with a combination of metformin, enalapril and MECP (200mg/kg) and combination of metformin, enalapril and MECP (400mg/kg) respectively. One group was kept as diabetic control. At the end of the study, body weight, kidney weight, and kidney hypertrophy index were evaluated. Biochemical and antioxidant parameters were evaluated. TGF-β levels in serum were estimated. Histopathology of the kidney was also studied. The combination therapy showed a significant increase in the body weight, lowered blood glucose levels and ameliorated kidney hypertrophy index in STZ induced diabetic nephropathy in rats. It also normalized the altered levels of serum and urine parameters. Histopathological evaluation revealed that combination therapy reduced the vacuolar degeneration of tubules. The results indicate that combination therapy of metformin, enalapril, and MECP has beneficial effects in management of diabetic nephropathy.