Oxidative stress contributes to defective antioxidant defenses, which may lead to type 2 diabetes (T2D). This study aimed to elucidate the T2D risks and antioxidant defenses by investigating the superoxide dismutase (SOD), catalase (CAT), vitamin A, and vitamin E status. We observed 102 participants aged 35–66 years from Sung Neon, Nakhon Ratchasima, Thailand. The blood samples were collected to measure the SOD, CAT, vitamin A, and vitamin E concentrations. The SOD and CAT activities were inversely associated with T2D risk. When compared with participants in the highest quartile of SOD and CAT, those in the lowest quartile for T2D risk obtained multivariable-adjusted odds ratios of 4.77 (SOD: 95% confident interval CI, 1.01–22.40; p = 0.047) and 4.22 (CAT: 95% CI, 1.07–16.60; p = 0.039). The possible influencing factors (e.g., physical activity, total cholesterol, and triglyceride) might mediate the association of SOD and CAT with T2D risk. Meanwhile, the relationship between vitamin A and vitamin E concentrations and T2D risk was insignificant. In conclusion, lower concentrations of antioxidant enzyme activity (SOD and CAT) may be an additional risk factor for T2D.