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<h4>Background</h4> Atherosclerotic risk starts at an early stage in adolescents and interventions on adolescents’ lifestyles are most important. The pandemic of obesity-related morbidities like atherosclerosis among young adults and atherosclerotic risk factors for middle-aged adolescents in India is known. Yet, there is a lack of cost-effective and integrated intervention programs to treat this important health problem. <h4>Objective</h4> The main objective of this study is to evaluate the effect of a 12-week structured interventional strategy program, containing integrated education and supervised physical activity interventions for middle-aged adolescents. <h4>Methods/design</h4> This will be a school-based pre-experimental one-group pre-post time-series research design. The sample size is estimated to include 154 adolescents of 10th to 12th grade; aged 15–17 years will be grouped as a single arm. Data will be collected from July 2021 to January 2022. The intervention duration will be 3 months. The following measures will be evaluated before, during, and after intervention: knowledge, body mass index, level of physical activity, dietary habits, and sedentary activity. <h4>Discussion</h4> We believe that the structured interventional strategy approach which includes education related to atherosclerosis, physical activity, dietary habits, and sedentary activity, and cost-effective physical activity training will be more effective in preventing atherosclerotic-related changes among middle-aged adolescents. Further, this kind of approach may be applied in similar study areas elsewhere in India. <h4>Trial registration</h4> Clinical Trials Registry—India (Registered Number: CTRI/2021/03/032271).