Background: The consumption of orange juice may lead to reduced oxidative stress and may enhance the antioxidant defense system. Objective: The aim was to evaluate the effects of the intake of orange juice containing either normal (NPJ) or high (HPJ) concentrations of polyphenols (299 and 745 mg/d, respectively) on the antioxidant defense system, oxidative stress biomarkers, and clinical signs of metabolic syndrome in 100 nonsmoking subjects who were either overweight or obese. Methods: A randomized, double-blind crossover study was conducted over two 12-wk periods with a 7-wk washout period. The effects on enzymatic and nonenzymatic blood antioxidant defense systems, urinary and plasma oxidative stress biomarkers, and clinical signs of metabolic syndrome were evaluated before and after an intervention with both of the orange juices. Paired t tests and linear mixed-effects models were used to evaluate the effects of juice, time, and interactions. Results: The intake of either NPJ or HPJ led to a decrease in urinary 8-hydroxy-2′-deoxyguanosine (NPJ: 935 +/- 134 to 298 +/- 19 ng/mg creatinine; HPJ: 749 +/- 84 to 285 +/- 17 ng/mg creatinine), 8-iso-prostaglandin F2 alpha (NPJ: 437 +/- 68 to 156 +/- 14 ng/mg creatinine; HPJ: 347 +/- 43 to 154 +/- 13 ng/mg creatinine), erythrocyte catalase, and glutathione reductase activities. A decrease was also observed in body mass index, waist circumference, and leptin (all P < 0.051) The NPJ intervention decreased systolic and diastolic blood pressures (systolic blood pressure: 128 +/- 1 to 124 +/- 2 mm Hg; diastolic blood pressure: 79 +/- 1 to 76 +/- 1 mm Hg), whereas the HPJ intervention increased erythrocyte superoxide dismutase (SOD) activity (17.7 +/- 1.5 to 23.1 +/- 1.7 U/mg hemoglobin). Conclusions: Our results show that the consumption of either NPJ or HPJ protected against DNA damage and lipid peroxidation, modified several antioxidant enzymes, and reduced body weight in overweight or obese nonsmoking adults. Only blood pressure and SOD activity were influenced differently by the different flavanone supplementations.