The COVID-19 pandemic caused by SARS-CoV-2 remains an international concern. Although there are drugs to fight it, new natural alternatives such as polyphenols are essential due to their antioxidant activity and high antiviral potential. In this context, this review reports the main findings on the effect of phenolic compounds (PCs) against SARS-CoV-2 virus. First, the proven activity of PCs against different human viruses is briefly detailed, which serves as a starting point to study their anti-COVID-19 potential. SARS-CoV-2 targets (its proteins) are defined. Findings from , and studies of a wide variety of phenolic compounds are shown, emphasizing their mechanism of action, which is fundamental for drug design. Furthermore, clinical trials have demonstrated the effectiveness of PCs in the prevention and as a possible therapeutic management against COVID-19. The results were complemented with information on the influence of polyphenols in strengthening/modulating the immune system. It is recommended to investigate compounds such as vitamins, minerals, alkaloids, triterpenes and fatty acids, and their synergistic use with PCs, many of which have been successful against SARS-CoV-2. Based on findings on other viruses, synergistic evaluation of PCs with accepted drugs against COVID-19 is also suggested. Other recommendations and limitations are also shown, which is useful for professionals involved in the development of efficient, safe and low-cost therapeutic strategies based on plant matrices rich in PCs. To the authors' knowledge, this manuscript is the first to evaluate the relationship between the antiviral and immunomodulatory (including anti-inflammatory and antioxidant effects) activity of PCs and their underlying mechanisms in relation to the fight against COVID-19. It is also of interest for the general population to be informed about the importance of consuming foods rich in bioactive compounds for their health benefits.