This review assessed sexual health and sexually transmitted infection (STI) burden among American Indian/Alaska Native (AI/AN) peoples within the context of current clinical and public health services. We conducted a review of published literature about sexual health and bacterial STIs among AI/AN populations in the United States using Medline (OVID), CINAHL (EbscoHost) and Scopus. Peer-reviewed journals published during 1 January 2005-2 December 2021 were included and supplemented by other publicly available literature. A total of 138 articles from reference lists met inclusion criteria, including 85 peer-review articles and 53 additional references. Results indicate a disproportionate burden of STIs is carried by AI/AN populations compared to non-Hispanic Whites. Risk for STIs in AI/AN people has origins in historical trauma and structural and social determinants of health. STI services are available for AI/AN populations, but many barriers to care exist. Community-based sexual health programming has been successful, but has thus far focused primarily on adolescents and young adults. A myriad of factors contributes to high rates of STIs among AI/AN populations. Longstanding disparities show a clear need to increase the availability of integrated, low-barrier STI prevention and treatment services. Implementation of multi-level (individual, physician, clinic, healthcare organisation, and/or community level), culturally relevant sexual health and STI interventions should be community-based and person-centred, acknowledge social determinants of health, and grounded in deep respect and understanding of AI/AN histories and cultures.