This community-based study explored the effectiveness of an after-school cultural-based intervention for Native American youth at risk for obesity. A standard health education after-school program served as the comparison control condition. Cherokee self-reliance (cultural identity), perceived stress, and obesity knowledge and related behaviors were the three outcome measures evaluated at baseline and immediate post-intervention. Findings revealed that participants who completed the cultural-based intervention had better results on the three outcome measures in comparison to the standard health education program.