Purpose: A systematic review and meta-analysis was conducted to assess the types of healthcare intervention programs offered to patients with multimorbidity and their effects on key psychosocial factors. Methods: For this systematic review and meta-analysis, we searched databases like Cochrane Library, PubMed, Embase, CINAHL RISS, KISS, etc. for studies published between January 1, 2009, and April 30, 2019. In total, 8,248 studies in English or Korean were reviewed. We included only randomized controlled trials or quasi-experimental studies that applied healthcare interventions and had major effects on the psychosocial factors in adult patients with multimorbidity. Methodological quality was assessed using Cochrane collaboration risk of bias tool. Meta-analysis was performed using the Review Manager 5.3 version to estimate the effect size. Results: We identified six randomized controlled trials and 1446 subjects were enrolled. The results reveal that healthcare interventions have an effect on self-rated health (SMD = 0.53 95 % CI: 0.26, 0.79, p < .001), reducing anxiety (SMD = -0.19 95 % CI: -0.36, -0.01, p = .030) and depression (SMD = -0.27 95 % CI: -0.44, -0.10, p = .002), and improving self-efficacy (SMD = 0.21 95 % CI: 0.06, 0.35, p = .005) for patients with multimorbidity. However, there was no significant effect on quality of life. Conclusion: Healthcare interventions had significant positive effects on self-rated health, anxiety, depression, and self-efficacy of patients with multimorbidity. These results are expected to serve as basic data for the development of a community-based integrated healthcare intervention program and health policy, especially for the vulnerable older population with multimorbidity.