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 ( β =−0.04, P =0.001), diabetes knowledge ( β =0.09, P =0.012), diet ( β =0.09, P <0.001), exercise ( β =0.10, P <0.001), blood sugar testing ( β =0.07, P =0.016), and foot care ( β =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.