Background <p>Oxidative stress plays a critical role in age-related pathophysiology, and postmenopausal women are particularly vulnerable due to hormonal and metabolic changes. Although dietary quality has been implicated in modulating oxidative balance, few studies have explored whether obesity mediates this relationship in this population, representing a novel perspective in dietary-oxidative research.</p> Objectives <p>This study aimed to examine the associations between dietary quality and oxidative stress among postmenopausal women using data from the National Health and Nutrition Examination Survey (NHANES), and to assess whether obesity mediates this relationship.</p> Methods <p>A total of 2,391 postmenopausal women from NHANES 2005–2020 were included. Dietary quality was assessed using the Healthy Eating Index (HEI-2015), Dietary Inflammatory Index (DII), and Composite Dietary Antioxidant Index (CDAI). Oxidative stress was measured using the Oxidative Balance Score (OBS), and obesity was evaluated by body mass index and waist circumference. Multivariable regression and mediation analysis were conducted to explore the relationships.</p> Results <p>Healthier diets (higher HEI and CDAI, lower DII) were significantly associated with better oxidative profiles and lower obesity indicators. Obesity was inversely associated with oxidative stress. Mediation analysis showed that obesity partially explained the association between diet and oxidative stress, indicating an indirect pathway linking dietary quality to oxidative status via adiposity.</p> Conclusions <p>Our findings reveal a significant mediating role of obesity in the relationship between diet and oxidative stress in postmenopausal women. These results underscore the importance of integrated dietary and weight management strategies—such as promoting antioxidant-rich diets and obesity prevention—in mitigating oxidative stress-related health risks in this population.</p>