INTRODUCTION: Poor menstrual health negatively impacts psychosocial and physical health, and subsequently leads to poor school outcomes, but the effort to improve adolescent girls' menstrual health in Tanzania remains fragmented. This study aimed to develop and pilot a scalable, comprehensive menstrual, sexual and reproductive health (MSRH) intervention within Tanzanian government structures to improve MSRH practices and perceptions and the overall school climate to ensure the psychosocial well-being and optimal school participation and performance among secondary schoolgirls. METHODS AND ANALYSIS: This study will be conducted in three phases. Phase I will be a formative research to iteratively refine an existing puberty and menstrual health intervention, and to collaboratively design strategies to embed the intervention into government structures thereby promoting scalability. In Phase II, we will pilot and evaluate the refined intervention and implementation strategies using a mixed-methods design to assess (1) feasibility, acceptability and sustainability; and (2) effect on MSRH practices and perceptions and the overall school climate. In Phase III, we will synthesise the research findings in collaboration with the national, regional and district government and non-government stakeholders. ETHICS AND DISSEMINATION: This pilot study will provide evidence-based recommendations for a comprehensive, complex menstrual and puberty intervention within secondary schools in Tanzania that can be further tested for broader effectiveness across a larger population. Papers, policy briefs and both regional/international conference presentations are planned to reach academic and non-academic groups. Protocol, tools and consent have been reviewed and approved by the independent Tanzanian national ethics committee (NIMR/HQ/R.8a/Vol.IX/3647) and the LSHTM Observational/Interventions Research Ethics Committee (LSHTM Ethics Ref: 22854). The project will involve adolescents, and procedures will be followed to ensure that we obtain permission and consent of parents and guardians and assent from all adolescents below 18 years of age that will be enrolled in the study.