Based on behavioral science assumptions, the main purpose of this study is to validate a theoretical model of the relationship between serious game play, patient empowerment and health-related behaviors. We first hypothesized that serious games for health enhanced patients' empowerment-related education; second, we expected that gender may influence such an educational model. To test our hypotheses, 124 Italian young diabetics (Mean age = 14.12 years old, SD = 2.14; 59.67% female) were involved in the research study named "Tako Dojo". After participating to a training session about the use of the serious game for diabetes, they filled in a questionnaire that included several scales of game experience, patient empowerment and adherence-related behaviors. Multiple regression analysis partially confirmed our hypotheses. First, it pointed out that serious game for health directly supported the patients' empowerment and their therapeutic adherence indirectly. Then, it showed that patients' gender influenced the game-based patient empowerment. To conclude, some relevant theoretical issues concerning the game-based patient education and practical implications about the game design in the healthcare contexts were highlighted.