IMPORTANCE Wisdom is a neurobiological personality trait made up of specific components, including prosocial behaviors, emotional regulation, and spirituality. It is associated with greater well-being and happiness. OBJECTIVE To evaluate the effectiveness of interventions to enhance individual components of wisdom. DATA SOURCES MEDLINE and PsycINFO databases were searched for articles published through December 31, 2018.STUDY ELIGIBILITY CRITERIA Randomized clinical trials that sought to enhance a component of wisdom, used published measures to assess that component, were published in English, had a minimum sample size of 40 participants, and presented data that enabled computation of effect sizes were included in this meta-analysis.DATA EXTRACTION AND SYNTHESIS Random-effect models were used to calculate pooled standardized mean differences (SMDs) for each wisdom component and random-effects meta-regression to assess heterogeneity of studies.MAIN OUTCOMES AND MEASURES Improvement in wisdom component using published measures.RESULTS Fifty-seven studies (N = 7096 participants) met review criteria: 29 for prosocial behaviors, 13 for emotional regulation, and 15 for spirituality. Study samples included people with psychiatric or physical illnesses and from the community. Of the studies, 27 (47%) reported significant improvement with medium to large effect sizes. Meta-analysis revealed significant pooled SMDs for prosocial behaviors (23 studies; pooled SMD, 0.43 [95% CI, 0.22-0.3]; P = .02), emotional regulation (12 studies; pooled SMD, 0.67 [95% CI, 0.21-1.12]; P = .004), and spirituality (12 studies; pooled SMD, 1.00 [95% CI, 0.41-1.60]; P = .001). Heterogeneity of studies was considerable for all wisdom components. Publication bias was present for prosocial behavior and emotional regulation studies; after adjusting for it, the pooled SMD for prosocial behavior remained significant (SMD, 0.4 [95% CI, 0.16-0.78]; P = .003). Meta-regression analysis found that effect sizes did not vary by wisdom component, although for trials on prosocial behaviors, large effect sizes were associated with older mean participant age (β, 0.08 [SE, 0.04]), and the reverse was true for spirituality trials (β, −0.13 [SE, 0.04]). For spirituality interventions, higher-quality trials had larger effect sizes (β, 4.17 [SE, 1.07]), although the reverse was true for prosocial behavior trials (β, −0.91 [SE 0.44]).CONCLUSIONS AND RELEVANCE Interventions to enhance spirituality, emotional regulation, and prosocial behaviors are effective in a proportion of people with mental or physical illnesses and from the community. The modern behavioral epidemics of loneliness, suicide, and opioid abuse point to a growing need for wisdom-enhancing interventions to promote individual and societal well-being.