Abstract Introduction Symptoms of anxiety and depression in Indian adolescents are common. Schools can be opportune sites for delivery of mental health interventions. India, however, is without a whole-school mental health approach. This article describes the study design for the Safeguarding Adolescent Mental Health in India (SAMA) project. The aim of SAMA is to co-design and feasibility test a suite of multi-component interventions across the intersecting systems of adolescents, schools, families and their local communities in India. Methods and analysis Our project will co-design and feasibility test four interventions to run in parallel in eight schools (three assigned to waitlist) in Bengaluru and Kolar in Karnataka, India. The primary aim is to reduce the prevalence of adolescent anxiety and depression. Co-design of interventions will build on existing evidence and resources. Interventions for adolescents at school will be universal, incorporating curriculum and social components. Interventions for parents and teachers will target mental health literacy, and also for teachers, training in positive behaviour practices. Intervention in the school community will target school climate to improve student mental health literacy and care. Intervention for the wider community will be via adolescent-led films and social media. We will generate intervention cost estimates, test outcome measures and identify pathways to increase policy action on the evidence. Ethics and dissemination Ethical approval has been granted by the National Institute of Mental Health Neurosciences Research Ethics Committee (NIMHANS/26th IEC (Behv Sc Div / 2020/2021)) and the University of Leeds School of Psychology Research Ethics Committee (PSYC-221). Certain data will be available on a data sharing site. Findings will be disseminated via peer-reviewed journals and conferences. Article Summary Strengths and Limitations A key strength of this study is its focus on depression and anxiety prevention, both of which are the common adolescent mental health problems in India. The study utilises a public mental health systems approach, which adopts a ‘person-in-context’ perspective and recognises multiple determinants of mental health. Extensive co-design of interventions will promote cultural relevance and acceptability by key stakeholders, including adolescents, teachers, parents and school communities. The Covid-19 pandemic makes this research more pertinent but may affect recruitment of the schools / adolescents or may lead to participation bias if the study processes are conducted online by excluding those with limited access or who lack technical skills. The opt-in approach to consent may lead to participation bias.