BACKGROUND: A better understanding of how multicomponent school-based interventions work and their effects on health and education outcomes are needed. This paper described the methods of the Movimente Program, a school-based intervention that aims to increase physical activity (PA) and decrease sedentary behavior (SB) among Brazilian students. METHODS: This is a cluster randomized controlled trial with adolescents from 7th to 9th grade in public schools from Florianopolis, Southern Brazil. After agreement, 6 schools were randomly selected to intervention or control groups (3 schools each), and all eligible students were invited to the study. The Movimente intervention program was performed during a school year and included 3 main components: Teacher training (including face-to-face meeting, social media platform, and handbook with lesson plans); improvements in the PA environment in school; and educational strategies. Control schools continued with their traditional schedule. Baseline (March/April 2017), postintervention (November/December 2017), and maintenance (June/July 2018) evaluations included PA and SB as primary outcomes (assessed by self-report and accelerometry). Secondary outcomes included psychosocial factors related to PA and SB (e.g., social support and self-efficacy), as well as health (e.g., quality of life and nutritional status) and education (e.g., academic achievement) outcomes. A program evaluation was performed based on the RE-AIM framework. Participants, intervention staffs, and evaluators were not blinded to group assignment, but a standardized evaluation protocol was applied independently of the trial allocation. RESULTS: Statistical analyses will include a multilevel approach for repeated measurements and mediation analysis. Any side effects of the intervention will be recorded. The sample size close to that expected (n = 1090) was reached (n = 999). The results of this trial will involve valuable information about the effect and the evaluation of a multicomponent intervention carried out in a middle-income country. CONCLUSION: By creating opportunities for adolescents to be active at school using multicomponent strategies, the Movimente program has the potential to enhance students health and academic performance which may encourage the school community (e.g., teachers, principals) to adopt the program. Also, this trial will provide evidence for practitioners, policy makers, and researchers on how multicomponent program may be implemented in a school setting. TRIAL REGISTRATION: The trial is registered at the Clinical Trial Registry (Trial ID: NCT02944318; date of registration: 18 October 2016).