IntroductionAdolescent onset substance use is associated with neurodevelopmental, social and psychological harms. Thus, alcohol and other drug prevention programmes are essential to promote health and well-being during this period. Schools are uniquely positioned to deliver such prevention programmes. The last decade has seen a large expansion of school-based alcohol and drug prevention programmes in Australia, warranting an update of the comprehensive review conducted by Teessonet alin 2012. This proposed review aims to (1) identify school-based substance use prevention programmes that have been trialled in Australia since 2011, (2) evaluate their efficacy and (3) identify intervention components associated with effectiveness. This will assist schools in identifying and adopting effective evidence-based programmes and inform future programme development, evaluation and policy.Methods and analysisStudies published from 2011 will be identified by searching the electronic databases PubMed, PsycINFO, Medline, Embase, ProQuest and Cochrane Library in addition to grey literature searches. Eligible studies will be controlled trials (including randomised controlled trials, cluster randomised controlled trials and quasi-experimental trials) of programmes measuring drug and alcohol related outcomes that are conducted in a school setting and have been trialled within Australia. Records will be independently screened for eligibility by two review authors, with disagreements being resolved by consensus or a third review author where necessary. Data extraction, risk of bias and study quality will also be completed independently by two review authors. A qualitative synthesis of all eligible studies will be presented. In addition, if there are sufficient data to combine studies, a random-effects meta-analysis will be conducted.Ethics and disseminationThis research is exempt from ethics approval as no primary data are collected, with work instead being carried out on published documents. The findings of this proposed review will be disseminated in a peer-reviewed journal and at conferences.PROSPERO registration numberCRD42021272959.