IMPORTANCE: Prosocial interventions encourage voluntary actions that benefit others. Community solidarity in response to the COVID-19 pandemic, expanding mutual aid programs, and health workforce issues have accelerated prosocial health interventions. OBJECTIVE: To investigate the association of prosocial interventions with health outcomes in clinical trials and observational studies. DATA SOURCES: In this systematic review and meta-analysis informed by the Cochrane Handbook for Systematic Reviews of Interventions, 5 databases (MEDLINE [via PubMed], Embase, CINAHL, PsycInfo, and Scopus) were searched from database inception through February 23, 2023. The search included terms for altruism and prosocial behaviors, health outcomes, and study type. STUDY SELECTION: Included studies, determined by multiple reviewers, compared health outcomes in a prosocial intervention group with a nonintervention group. DATA EXTRACTION AND SYNTHESIS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline, data extraction and synthesis captured quantitative and qualitative data. To pool data from quantitative studies, random-effects meta-analyses were used to estimate the impact of prosocial interventions. To combine data from quantitative and qualitive studies, data were transformed into qualitative narratives using meta-aggregation. MAIN OUTCOMES AND MEASURES: The main outcome was whether prosocial interventions were associated with improved health outcomes. Barriers to and facilitators of implementation of these interventions were assessed. RESULTS: The search identified 5229 citations; 30 studies were included in the synthesis. Studies indicated that prosocial interventions were associated with positive health outcomes for givers (17 studies [56.7]) and recipients (8 [26.7%]). Prosocial interventions included acts of kindness (12 studies [40.0%]), cash gifts (7 [23.3%]), pay-it-forward approaches (6 [20.0%]), and expressions of kindness (5 [16.7%]). Improvements were reported in depression, testing for sexually transmitted diseases, vaccine uptake, physical activity, and individual biomarkers. Data from 6 studies (20.0%) demonstrated that pay-it-forward approaches were associated with increased uptake of diagnostic tests or vaccines among vulnerable groups (moderate certainty of evidence). Data from 14 studies (46.7%) suggested that community connectedness facilitated prosocial interventions. Shared vulnerabilities among groups (eg, sexual minority individuals, older adults) may provide a context for collective mobilization to improve health in local communities. CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found that prosocial interventions were associated with improved health outcomes among vulnerable groups and have been useful for addressing health disparities. Further research is needed to develop and evaluate prosocial interventions.