The aim of this meta-analysis of randomized controlled trials was to evaluate the effect of hydroxychloroquine on glucose control.Randomized controlled trials examining the impact of hydroxychloroquine on glycemic markers were searched in PubMed, Web of Science, Scopus, and Google Scholar databases. Meta-analysis was performed using a random-effects model and sensitivity analysis through the leave-one-out method.Meta-analysis revealed a significant reduction of fasting glucose (WMD: - 8.05 mg/dl; 95% CI: - 11.17, - 4.93; I2 = 75%; p ˂0.0001), 2-h postprandial glucose (WMD: - 15.52 mg/dl; 95% CI: - 20.61, - 10.42; I2 = 53%; p ˂0.00001), and glycated hemoglobin (HbA1c) values (WMD: - 0.19%, 95% CI: - 0.37, - 0.02; I2 = 94%; p = 0.03) after hydroxychloroquine treatment. Otherwise, meta-analysis showed no significant effect of hydroxychloroquine on insulin levels (WMD: 16.52 μUI/ml; 95% CI: - 16.35, 49.40; I2 = 90%; p = 0.32) and HOMA-β (WMD: - 14.62; 95% CI: - 45.84, 16.59; I2 = 0%; p = 0.36).The present meta-analysis revealed that treatment with hydroxychloroquine improves glucose control through the reduction of fasting glucose, 2-h postprandial glucose, and HbA1c values. Given that the effect of hydroxychloroquine on beta-cell function is based only on two clinical trials, it is not possible to draw definitive conclusions.© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.