BACKGROUND: The problem of loneliness has garnered increased attention from policymakers, payors, and providers due to higher rates during the pandemic, particularly among seniors. Prior systematic reviews have in general not been able to reach conclusions about effectiveness of interventions. METHODS: Computerized databases were searched using broad terms such as loneliness or lonely or social isolation or social support from Jan 1, 2011 to June 23, 2021. We reference mined existing systematic reviews for additional and older studies. The Social Interventions Research & Evaluation Network database and Google were searched for gray literature on Feb 4, 2022. Eligible studies were RCTs and observational studies of interventions to reduce loneliness in community-living adults that used a validated loneliness scale; studies from low- or middle-income countries were excluded, and studies were excluded if restricted to populations where all persons had the same disease (such as loneliness in persons with dementia). RESULTS: A total of 5971 titles were reviewed and 60 studies were included in the analysis, 36 RCTs and 24 observational studies. Eleven RCTs and 5 observational studies provided moderate certainty evidence that group-based treatment was associated with reduced loneliness (standardized mean difference for RCTs =  - 0.27, 95% CI - 0.48, - 0.08). Five RCTs and 5 observational studies provided moderate certainty evidence that internet training was associated with reduced loneliness (standardized mean difference for RCTs =  - 0.22, 95% CI - 0.30, - 0.14). Low certainty evidence suggested that group exercises may be associated with very small reductions in loneliness. Evidence was insufficient to reach conclusions about group-based activities, individual in-person interactions, internet-delivered interventions, and telephone-delivered interventions. DISCUSSION: Low-to-moderate certainty evidence exists that group-based treatments, internet training, and possibly group exercises are associated with modest reductions in loneliness in community-living older adults. These findings can inform the design of supplemental benefits and the implementation of evidence-based interventions to address loneliness. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO ( CRD42021272305 ).