Introduction: Nephropathy is defined as rational loss of renal function related with glomerulosclerosis and declining glomerular filtration rate. Inflammation and oxidative stress play a critical role in nephropathy. Plantago major has antioxidant effects. The aim of present study is the investigation of the effect of Plantago major hydro-alcoholic extract on the oxidative stress and renal function in kidney of rat. Methods: Rats were divided into five groups: control (Co), doxorubicin (DOX), doxorubicin+vitamin E (DOX+Vit E), 600mg/kg Plantago major (PM)+doxorubicin (PM600+DOX), 1200mg/kg Plantago major (PM)+doxorubicin (PM1200+DOX). DOX (5mg/kg, IV), Vit E and PM extract (600 and 1200mg/kg, PO) were administrated for 35 days. Finally, urine, blood samples and renal tissue were collected to measurement of redox markers, functional parameters and renal index percentage. Results: The renal superoxide dismutase (SOD) activity, total thiol and functional parameters significantly reduced and malondialdehyde (MDA) concentration increased in DOX group in comparison with control group. The renal SOD, catalase activities and total thiol content were significantly increased and MDA level decreased in PM treated groups along with DOX group in comparison with DOX group. The functional parameters significantly enhanced in treated groups with PM in comparison with the DOX group. The extract did not relive enhanced % renal index induced by DOX. Conclusion: Hydro-alcoholic extracts of PM, specially at its high dose led to an improvement in DOX-induced renal function and oxidative stress.