The COVID-19 outbreak seems to be the most dangerous challenge of the third millennium due to its highly contagious nature. Amongst natural molecules for COVID-19 treatment, the flavonoid molecule quercetin (QR) is currently considered one of the most promising. QR is an active agent against SARS and MERS due to its antimicrobial, antiviral, anti-inflammatory, antioxidant, and some other beneficial effects. QR may hold therapeutic potential against SARS-CoV-2 due to its inhibitory effects on several stages of the viral life cycle. In fact, QR inhibits viral entry, absorption, and penetration in the SARS-CoV virus, which might be at least partly explained by the ability of QR and its derivatives to inhibit 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro). QR is a potent immunomodulatory molecule due to its direct modulatory effects on several immune cells, cytokines, and other immune molecules. QR-based nanopreparations possess enhanced bioavailability and solubility in water. In this review, we discuss the prospects for the application of QR as a preventive and treatment agent for COVID-19. Given the multifactorial beneficial action of QR, it can be considered a very valid drug as a preventative, mitigating, and therapeutic agent of COVID-19 infection, especially in synergism with zinc, vitamins C, D, and E, and other polyphenols.