The objective of the review is to determine the effectiveness of telehealth versus in-person care on health care utilization, health-related quality of life, and well-being in homebound populations. Globally, an increasing number of people are becoming homebound. These individuals experience high levels of social isolation and deterioration of their well-being. Reports from homebound people and recent publications suggest that this cohort may benefit from accessing telehealth solutions from their homes to treat and prevent serious issues affecting their health and well-being. This review will synthesize the evidence on the effectiveness of telehealth compared to standard care (in-person care) on health care utilization, health-related quality of life, and well-being in homebound populations. Studies including people living in community settings, whose daily life is physically limited to the boundary of their homes because of their ongoing health, energy, and psychosocial or socio-functional impairments will be considered for inclusion. This review will consider relevant, peer-reviewed primary experimental and quasi-experimental studies, with no limit on language or date. Databases to be searched include MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, LILACS, JBI Evidence Synthesis (hand-searched for further studies), and Web of Science. Two independent reviewers will be involved in study selection and data extraction. Eligible studies will be critically appraised for methodological quality using the relevant JBI critical appraisal checklists, and statistical meta-analysis will be done (where possible). Findings will be presented in narrative form. PROSPERO CRD42021289578.