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Background: The undergraduate medical training programme is demanding and rigorous. This underlines the importance of a peer mentorship strategy to improve the well-being, self-determination, school connectedness, and performance of struggling medical and nursing students. This study is aimed at identifying struggling medical and nursing students using two cumulative continuous assessment test (CAT) scores, assess their subjective vitality and school engagement and evaluate the impact of the peer mentorship intervention on them., Methods: The study will adopt a mixed-methods approach and will be conducted in the medical colleges of Nnamdi Azikiwe University, Awka, Nigeria, and the University of Rwanda. Three instruments will be used: The subjective Vitality Scale (SVS), the University Student Engagement Inventory (USEI), and the academic records of the students before and after the commencement of the intervention programme. The consenting least-performing medical and nursing students identified by their low CAT scores (below 45%) in basic medical sciences will be selected for study in each institution. The outcome measures will include students' CAT scores, subjective vitality, and school engagement scores. The data will be analysed both quantitatively and qualitatively. Thematic content analysis will be adopted in the analysis of the responses generated from the focus group discussion. The mean ± standard deviation or median and interquartile range statistic will be adopted for the quantitative data., Discussion: Given the paucity of data on struggling medical and nursing students in Nigeria and Rwanda, this research was designed to help in exploring evidence-based interventions to improve and prevent poor subjective well-being of struggling students. The study is expected to fill these knowledge gaps., Trial Registration: Pan African Clinical Trial registry, PACTR202405546896613, registration date: 27 th May, 2024. This proposal has been supported by grant 1R25TW011217 from the US National Institutes of Health (NIH)/Fogarty International Center (FIC) which also includes co-funds from the U.S. Department of State's Office of the U.S. Global AIDS Coordinator and Health Diplomacy (S/GAC) and the President's Emergency Plan for AIDS Relief (PEPFAR) to the African Forum for Research and Education in Health (AFREhealth). The Grant Principal Investigators are Profs. Nelson K.Sewankambo (contact PI), Prisca Adejumo, Jean Bisimwa Nachega, Fatima Suleman., (© 2024. The Author(s).)