ObjectiveTo systematically review the efficacy and safety of Molnupiravir in the treatment of COVID-19. MethodsThe CNKI, VIP, WanFang Data, PubMed, Web of Science, Cochrane Library, and Epistemonikos COVID-19 L·OVE databases were electronically searched to collect randomized controlled trials (RCTs) related to Molnupiravir therapy for COVID-19 from inception to July, 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.4 software. ResultsA total of 9 RCTs involving 32 086 patients were included. The meta-analysis results revealed that no significant differences were observed in the 28-29 day hospitalization rate, the 28-29 day mortality rate, 14-15 day PCR test conversion rate, or adverse event incidence between the two groups. However, there was a significant increase in adverse events related to four types of systemic organ diseases in the Monolaurin group. Conclusion Current evidence shows that the safety profile of Monolaurin and its potential benefits for COVID-19 patients with a high risk of progressing to severe illness is unclear. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.