Diabetes mellitus (DM) is a chronic‐degenerative disease characterized by chronic hyperglycemia. Chronic hyperglycemia has been demonstrated to stimulate the excessive production of reactive oxygen species as well as a decrease in the activity of antioxidant defense systems, leading to a state of oxidative stress. Certain organs are mostly exposed to oxidative damage due to the fact that they exhibit an independent insulin glucose uptake and their high energy demand, among which the kidney is included, leading to a progressive development of diabetic nephropathy. One alternative is the use of medicinal plants. Potentilla indica, commonly called “false strawberry” or “Indian strawberry”, is a medicinal herb widely used in traditional Asian medicine for the treatment of various diseases including DM, due to the biological activity exhibited by the content of secondary metabolites (SM) that it presents, and which can be extracted by using solvents of different polarity, where the SM extracted are found depending on the polarity of the solvent used. The present study aims to evaluate the antioxidant activity exerted by the ethyl acetate extract of Potentilla indica, in vitro and using streptozotocin‐induced Wistar diabetic rats as a biological model. To meet the objective, the in vitro antioxidant effect of the extract was first evaluated and a phytochemical analysis was carried out. Subsequently, the extract was administered orally with a dose of 25 mg/Kg of weight for 60 days. At the end of the treatment, the rats were sacrificed, the serum was collected for the determination of glucose levels, as well as the renal function markers: urea nitrogen, creatinine, and uric acid. Subsequently, the kidneys were dissected to obtain the homogenate in which the activity of the antioxidant enzyme catalase (CAT) was determined, likewise the isolation of the kidney mitochondria was carried out where the activity of complexes I, II, III and IV of ETC was evaluated, ROS production, lipid peroxidation levels as a biomarker of oxidative damage, as well as mitochondrial enzymatic antioxidant biomarkers: superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px).The in vitro results showed a powerful antioxidant activity as well as a high content of flavonoids. The in vivo results after the administration of the ethyl acetate extract of P. indica, showed that the extract did not present a hypoglycemic effect, however, it prevented the excessive loss of body weight in diabetic rats. In addition, it improved the activity of mitochondrial respiratory complexes, decreased ROS production and lipid peroxidation in kidney mitochondria, as well as increased activity of the antioxidant enzymes CAT, SOD and GSH‐Px. In conclusion, our data suggest that the Potentilla indicaethyl acetate extract exhibits antioxidant activity both in vitro and in the kidneys of STZ‐induced diabetic rats.