The widespread dissemination of misinformation has become a global concern. A recommended solution is to improve people’s ability to discern true from false information through appropriate media literacy education programs. This meta-analysis quantitatively synthesized the results of 49 experimental studies ( N = 81,155) that examined the efficacy of media literacy interventions in mitigating misinformation. This study finds that media literacy interventions generally improve resilience to misinformation ( d = 0.60). Specifically, the interventions reduce belief in misinformation ( d = 0.27), improve misinformation discernment ( d = 0.76), and decrease misinformation sharing ( d = 1.04). Moreover, media literacy interventions have stronger effects (1) when multiple sessions rather than a single session are implemented, (2) in high (vs. low) uncertainty avoidance cultures, and (3) among college students than among adults recruited from online crowdsourcing platforms (e.g., Amazon Mechanical Turk). These findings enrich our understanding of inoculation theory and provide valuable guidance for the design of future media literacy intervention programs.