IntroductionThe World Health Organization (WHO) advocates for the strengthening of education and training in infection prevention and control (IPC) in higher educational institutions (HEIs). This is fundamental to ensure health science students are confident and competent in clinical practice.AimExplore the preparedness of undergraduate health science students for IPC practice.Search strategyThe PubMed, Cumulative Index to Nursing and Allied Health Literature, EMBASE, ProQuest, Scopus, Web of Science, ClinicalKey, and Google Scholar databases and grey literature will be searched for relevant articles.Inclusion criteriaQuantitative, and mixed methods studies on teaching and learning, technological methods, strengths and limitations, and challenges of IPC practice in HEI undergraduate curricula.Participant characteristicsUndergraduate health science students including medical, nursing, pharmacy, dental, physiotherapy, radiology, medical imaging, and paramedicine.Setting and time frameStudies published anywhere in the world, in English, and from 2010 to 2023.Search termsPreparedness, health science students, infection prevention and control, technology, higher education institutions.Data extractionThe data extracted will be recorded on a data extraction form.Assessment of risk of biasThis will be conducted according to the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Ethics and disseminationNo ethical approval was required for this protocol. Interim findings will be presented at relevant local and international conferences and a manuscript will be published in a peer reviewed journal.DiscussionThis systematic review will provide a baseline for recommendations for developing innovative ways to improve IPC teaching and learning in HEI.