INTRODUCTION: As educators and health professionals, school nurses are in an optimal position to improve and advocate for adolescent reproductive and sexual health. This report outlines a protocol for a systematic review to synthesize evidence on the effects of school nurse-led education interventions and barriers and facilitators to implementing the interventions to improve students' knowledge, attitudes and behaviours related to sexual and reproductive health in high-income countries. METHODS AND ANALYSIS: We will develop a protocol to systematically review school nurse-led education interventions aimed at promoting adolescent sexual and reproductive health. This protocol will be based on the methodology of the ETHICS AND DISSEMINATION: This review will synthesise publicly available resources and does not require ethical approval. The findings will provide insights into how school nurses can improve students' sexual and reproductive health. The results will be disseminated through peer-reviewed publications, reports and academic conferences. PROSPERO REGISTRATION NUMBER: CRD42022347625.