Social isolation and loneliness (SIL) are public health challenges that disproportionally affect individuals who experience structural and socio-economic exclusion. The social and health outcomes of SIL for people with experiences of being unhoused have largely remained unexplored. Yet, there is limited synthesis of literature that focused on SIL to appropriately inform policy and facilitate targeted social interventions for people with homelessness experience. The aim of this scoping review is to synthesize evidence on SIL among people with lived experience of homelessness and explore how it negatively impacts their wellbeing. We carried out a comprehensive literature search from Medline, Embase, Cochrane Library, PsycINFO, CINAHL, Sociological Abstracts, and Web of Science's Social Sciences Citation Index and Science Citation Index for peer-reviewed studies published between 2000 to on January 3rd, 2023. Studies went through title, abstract and full-text screening conducted independently by at least two reviewers. Included studies were then analyzed and synthesized to identify the conceptualizations of SIL, measurement tools and approaches, prevalence characterization, and relationship with social and health outcomes. The literature search yielded 5,294 papers after removing duplicate records. After screening, we retained 27 qualitative studies, 23 quantitative studies and two mixed method studies. SIL was not the primary objective of most of the included articles. The prevalence of SIL among people with homelessness experience varied from 25–90% across studies. A range of measurement tools were used to measure SIL making it difficult to compare results across studies. Though the studies reported association between SIL, health, wellbeing, and substance, we found substantial gaps in the existing literature. Most of the quantitative studies were cross-sectional, and no study reported on interventions that targeted SIL as a main or secondary outcome. More studies are needed to better understand SIL among this population and to build evidence for actionable strategies and policies to address its social and health impacts.