The objectives of this review were to determine the effectiveness of socially assistive technologies for improving depression, loneliness, and social interaction among residents of long-term care (LTC) homes, and to explore the experiences of residents of LTC homes with socially assistive technologies. Globally, the number of older adults (≥ 65 years) and the demand for LTC services are expected to increase over the next 30 years. Individuals within this population are at increased risk of experiencing depression, loneliness, and social isolation. The exploration of the extent to which socially assistive technologies may aid in improving loneliness and depression while supporting social interactions is essential to supporting a sustainable LTC sector. This mixed methods systematic review included studies on the experiences of older adults in LTC homes using socially assistive technologies, as well as studies on the effectiveness of these technologies for improving depression, loneliness, and social interaction. Older adults were defined as people 65 years of age and older. We considered studies examining socially assistive technologies, such as computers, smart phones, tablets, and associated applications. A JBI mixed methods convergent, segregated approach was used. CINAHL (EBSCOhost), MEDLINE (Ovid), Embase, APA PsycINFO (EBSCOhost), and Scopus databases were searched on January 18, 2022, to identify published studies. The search for unpublished studies and gray literature included ProQuest Dissertations and Theses Global, Open Access Theses and Dissertations, Google, and the websites of professional organizations associated with LTC. No language or geographical restrictions were placed on the search. Titles, abstracts, and full texts of included studies were screened by 2 reviewers independently. Included studies underwent quality appraisal and data extraction. Quantitative and qualitative data findings were analyzed separately and then integrated. Where possible, quantitative data were synthesized using comparative meta-analyses with a fixed-effects model. From 12,536 records identified through the search, 14 studies were included. Quantitative (n=8), mixed methods (n=3), and qualitative (n=3) approaches were used in the included studies, with half (n=7) using quasi-experimental designs. All studies received moderate to high-quality appraisal scores. Comparative meta-analyses for depression and loneliness scores did not find any significant differences, and narrative findings were mixed. Qualitative meta-aggregation identified 1 synthesized finding (Matching technology functionality to user for enhanced well-being) derived from 2 categories (Enhanced sense of well-being, and Mismatch between technology and resident ability). Residents' experiences with socially assistive technologies, such as videoconferencing, encourage a sense of well-being, although quantitative findings related to depression and loneliness reported mixed impact. Residents experienced physical and cognitive challenges in learning to use the technology and required assistance. Future work should consider the unique needs of older adults and LTC home residents in the design and use of socially assistive technologies. PROSPERO CRD42021279015.