Currently, antiviral drugs and/or vaccines are not yet available to treat or prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we narrated the available data, from credible publishers, regarding the possible role of polyphenols and natural extracts-containing polyphenols in the prevention of coronavirus disease 2019 (COVID-19), and their immune-boosting properties. It was revealed that polyphenols could be considered as promising biologically active substances for the prevention of COVID-19. The underlying potential mechanism behind this action is mostly due to the antiviral activities and the immune-regulation functions of polyphenols against COVID-19-infections. Antivirus polyphenolic-based medications can mitigate SARS-CoV-2-enzymes, which are vital for virus duplication and infection. It was also found that triterpenoid, anthraquinone, flavonoids, and tannins are possible keys to scheming antiviral therapies for inhibiting SARS-CoV-2-proteases. The identified pharmacophore structures of polyphenols could be utilized in the explanation of novel anti-COVID-19 designs. The advantage of using mixtures containing polyphenols is related to the high-safety profile without having major side-effects, but further randomized controlled trials are required in the upcoming studies. © 2021 Elsevier Ltd