Understanding the dimensions of internal and external validities (e.g., using the RE-AIM model: Reach, Effectiveness/Efficacy, Adoption, Implementation, and Maintenance) of school interventions is important to guide research and practice in this context. The aim of this systematic review protocol is to synthesize evidence on the RE-AIM dimensions in interventions based on the Health Promoting School (HPS) approach from the World Health Organization (WHO) in Latin America. Studies of interventions based on HPS-WHO that were carried out in Latin America involving the population of 5 to 18-year-olds will be eligible. Searches in nine electronic databases, a study repository, the gray literature, and the retrieved articles’ reference lists will be performed, without year or publication language limits. Study selection and data extraction will be conducted by independent researchers. Data on intervention implementation will be summarized in categories of HPS-WHO actions: (1) school curriculum, (2) changes in the social and/or physical environment of schools, and (3) actions with families and the community. A previously validated tool will be used to summarize the information on the dimensions of the RE-AIM model. The strengths and limitations of the included studies will be evaluated using the Critical Appraisal Skills Program (CASP) tool, and the confidence level of evidence will be assessed according to the GRADE CERQual tool.