Background: In comparison to the general population, people who are homeless have poorer health and health-related outcomes, including for vaccine-preventable diseases. Vaccination is safe, effective and cost-effective, and many vaccination guidelines specifically recommend vaccination in people who are homeless. This systematic review will identify interventions which are effective in delivering vaccination to, and/or at improving vaccination rates in, people who are homeless. Methods/Design: This systematic review is presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches will be undertaken on eight electronic databases, using combinations of search terms and subject headings or index terms. Citation chaining will also be undertaken. Literature will be screened for relevance against inclusion/exclusion criteria firstly by title/abstract and secondly by full text. The selected studies will be assessed for quality using an evidence-based tool appropriate to their methods. Data relevant to the topic will be extracted and examined using meta-analysis and narrative synthesis. Discussion: This systematic review will address an important gap in the literature about vaccination in people who are homeless. The review’s findings are particularly relevant considering the current coronavirus disease (COVID-19) pandemic, which is likely to be managed through vaccination.