Background: Evidence suggests that empowerment is an important factor to address everyday aspects of dealing with a chronic disease. This study evaluated the effect of diabetes empowerment on medication adherence and self-care behaviors in adults with type 2 diabetes. Subjects and Methods: Data on 378 subjects with type 2 diabetes recruited from two primary care clinics in the southeastern United States were examined. Previously validated scales were used to measure diabetes empowerment, medication adherence, diabetes knowledge, and diabetes self-care behaviors (including diet, physical activity, blood sugar testing, and foot care). Multiple linear regression was used to assess the independent effect of diabetes empowerment on medication adherence and self-care behaviors controlling for relevant covariates. Results: Eighty-three percent were non-Hispanic blacks, 69% were women, 22% were 65 years or older, 68% were not married, 26% had less than high school education, 60% were unemployed, 39% were uninsured, and 47% had a yearly income <$10,000. Empowerment had significant correlations with medication adherence (r = 0.17, P < 0.003), diabetes knowledge (r = 0.16, P = 0.007), diet (r = 0.24, P < 0.001), exercise (r = 0.25, P < 0.001), blood sugar testing (r = 0.12, P = 0.043), and foot care (r = 0.18, P = 0.002). In the regression model, diabetes empowerment was significantly associated with medication adherence (beta = -0.04, P = 0.001), diabetes knowledge (beta = 0.09, P = 0.012), diet (beta = 0.09, P < 0.001), exercise (beta = 0.10, P < 0.001), blood sugar testing (beta = 0.07, P = 0.016), and foot care (beta = 0.08, P = 0.001). Conclusions: In this sample, diabetes empowerment was related to better diabetes knowledge, medication adherence and improved self-care behaviors. Emphasis on empowerment and self-efficacy is relevant to improve outcomes in the management of diabetes.