Background: Weight stigma is prevalent among adolescents and can negatively impact physical and mental health. This study examined the effects of a combined physical activity and attitude education intervention on weight stigma and related outcomes among high school students. Methods: A randomized controlled trial was conducted with 524 high school students. The intervention group received a 3-month program combining physical activity education and anti-stigma attitude training. Outcomes measured included the use of weight loss medication, physical activity levels, weight loss, and depressive symptoms. Results: The intervention group showed significant decreases in weight loss medication use and depressive symptoms, and increases in physical activity levels compared to the control group. No significant differences were observed in weight loss between groups. Gender differences were noted, with girls showing greater improvements in physical activity. Implications: Findings support integrating weight stigma reduction strategies into school health programs. Schools should adopt attitude modification approaches, promote inclusive physical activities, and foster social support to address weight stigma and associated depression symptoms. Conclusions: Combining physical activity and attitude education can effectively reduce weight stigma and improve health behaviors among high school students. Future research should explore long-term effects and tailored approaches for different student populations.