Coronavirus disease (COVID-19) affects both the respiratory system and the body as a whole. Natural molecules, such as flavonoid quercetin, as potential treatment methods to help patients combat COVID-19. The aim of this systematic review and meta-analysis is to give a comprehensive overview of the impact of quercetin supplementation on inflammatory factors, hospital admission, and mortality of patients with COVID-19. The search has been conducted on PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library using relevant keywords until August 25, 2023. We included randomized controlled trials (RCTs) comparing COVID-19 patients who received quercetin supplementation versus controls. We included five studies summarizing the evidence in 544 patients. Meta-analysis showed that quercetin administration significantly reduced LDH activity (standard mean difference (SMD): -0.42, 95% CI: -0.82, -0.02, I 2 = 48.86%), decreased the risk of hospital admission by 70% (RR: 0.30, 95% CI: 0.14, 0.62, I 2 = 00.00%), ICU admission by 73% (RR: 0.27, 95% CI: 0.09, 0.78, I 2 = 20.66%), and mortality by 82% (RR: 0.18, 95% CI: 0.03, 0.98, I 2 = 00.00%). No significant changes in CRP, D-dimmer, and ferritin were found between groups. Quercetin was found to significantly reduce LDH levels and decrease the risk of hospital and ICU admission and mortality in patients with COVID-19 infection.