The present study evaluated the effect of Prosthechea karwinskii leaves extract on antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in a model of obese rats with insulin resistance to know its nutraceutical potential on insulin resistance and oxidative stress. Obesity and insulin resistance were induced in rats by administering 40% sucrose in water. Once the model was established, four groups were evaluated (control, obese, obese administered with extract, and obese administered with metformin), and the indices of insulin resistance and the activity of antioxidant enzymes were measured. In addition, compounds in the extract were identified with UHPLC-ESI-qTOF-MS/MS. The glucose, insulin, triglycerides, and insulin resistance indicators (HOMA-IR and TyG) increased in obese rats. The activity of the antioxidant enzymes evaluated increased in the obese group, apparently as an adaptive response to oxidative stress to inhibit reactive oxygen species formed by hyperglycemia. Administration of P. karwinskii extract and metformin reduced glucose, insulin, triglyceride levels, insulin resistance indicators and antioxidant enzymes to values like those of the control group. This study shows the nutraceutical potential of P. karwinskii extract as an ingredient in the formulation of food supplements or functional foods to help treat diseases related to insulin resistance and oxidative stress.