Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The aim of the study was to determine the antiviral effect of the administration of zinc in COVID-19 patients. A literature search was performed in P Web of Science, PubMed, Scopus and Cochrane databases from 1 January 2020–22 August 2022. In addition, reference lists of the included articles and their related citations in PubMed were also reviewed for additional pertinent studies. A total of 9 eligible studies were identified. In-hospital mortality in zinc supplementation patients, and patients treated without zinc, varied and amounted to 21.6% vs. 23.04% difference (OR= 0.71; 95% CI: 0.62–0.81; p< 0.001). 28-day to 30-day mortality in patients treated with zinc was 7.7%, compared to 11.9% for patients treated without zinc (OR= 0.61; 95% CI: 0.35–1.06; p= 0.08). In-hospital adverse events among patients treated with and without COVID-19 did not show any statistically significant differences in relation to acute kidney injury occurrence (12.8% vs. 12.4%, respectively; OR= 0.63; 95% CI: 0.19–2.12; p= 0.45, as well as need for mechanical ventilation (13.2% vs. 14.1%; OR= 0.83; 95% CI: 0.52–1.32; p= 0.43). Zinc supplementation is associated with lower COVID-19 in-hospital mortality. Additionally, it is risk-free in COVID-19 patients since there have been no negative side effects, such as acute renal damage or the requirement for mechanical ventilation compared to patients without COVID-19. Due to scientific evidence and the role it represents in the human body, zinc supplementation should be taken into consideration for COVID-19 patients as an adjunct therapy.