Coronavirus disease 2019 (COVID‑19), a systemic illness caused by severe acute respiratory distress syndrome 2 (SARS‑CoV‑2), has triggered a worldwide pandemic with symptoms ranging from asymptomatic to chronic, affecting practically every organ. Melatonin, an ancient antioxidant found in all living organisms, has been suggested as a safe and effective therapeutic option for the treatment of SARS‑CoV‑2 infection due to its good safety characteristics and broad‑spectrum antiviral medication properties. Melatonin is essential in various metabolic pathways and governs physiological processes, such as the sleep‑wake cycle and circadian rhythms. It exhibits oncostatic, anti‑inflammatory, antioxidant and anti‑aging properties, exhibiting promise for use in the treatment of numerous disorders, including COVID‑19. The preventive and therapeutic effects of melatonin have been widely explored in a number of conditions and have been well‑established in experimental ischemia/reperfusion investigations, particularly in coronary heart disease and stroke. Clinical research evaluating the use of melatonin in COVID‑19 has shown various improved outcomes, including reduced hospitalization durations; however, the trials are small. Melatonin can alleviate mitochondrial dysfunction in COVID‑19, improve immune cell function and provide antioxidant properties. However, its therapeutic potential remains underexplored due to funding limitations and thus further investigations are required.