<p>Carcinogenesis is a web of complex changes in the dynamics of cells and their environment. These changes have been systemically explained as hallmarks of oral cancer. Each of the hallmarks of cancer can be specifically targeted for therapy. Natural products draw leverage in target therapy owing to their multi-faceted molecular targeting, in addition to lower risk of adverse effects. Hesperetin has shown promising results in reversing molecular carcinogenic alterations in various cancers. Hesperetin is a natural flavonoid, an aglycone of hesperidin. It is one of the most important bioflavonoids in lemons and sweet oranges. In this article, by drawing parallels between the mechanism of action of hesperetin in the prevention and treatment of various other cancers and the molecular mechanisms of oral cancer carcinogenesis, we discuss in detail the molecular target mechanisms through which hesperetin may help in the prevention of oral cancer. We have also identified research gaps where molecular targets of hesperetin have not yet been explored for oral cancer.</p>