Oxidative stress has been implicated in the development of gynecologic cancers, including endometrial cancer. This study investigated serum antioxidant levels and oxidative stress markers in 200 women with endometrial cancer compared to 200 healthy, age- and body mass index-matched controls. Antioxidants such as vitamin C, glutathione, and ceruloplasmin were significantly lower in cancer patients, while markers of oxidative stress, including malondialdehyde, peroxynitrite, gamma-glutamyl transferase, superoxide dismutase, and catalase, were markedly elevated. Notably, antioxidant levels showed inverse correlations with several oxidative markers, and lower levels of glutathione and vitamin C were independently linked to higher endometrial cancer risk. These findings suggest that redox imbalance plays a critical role in endometrial carcinogenesis and that antioxidant profiles may aid in risk assessment and early detection strategies.