<p>Bioaccessibility (the fraction of ingested drug/bioactive compounds that undergoes metabolic processes, systemic absorption, and tissue distribution) and bioavailability (the fraction of drug/bioactive compounds available in systemic circulation) are significant issues and challenges that impact bioactivities and therapeutic responses for polyphenolic compounds. Polyphenolic compounds, abundantly available in natural sources, are of great interest in pharmaceutical, nutraceutical, and functional food applications due to their unique therapeutic and potential health benefits in humans. However, free polyphenolic compounds are susceptible to numerous exogenous factors, including heat, light, oxygen, and UV rays, as well as endogenous factors such as gastric pH, solubility, diffusion, elimination, complexation, hydrolysis, oxidation, and reduction, which ultimately affect their bioaccessibility and bioavailability. Encapsulation is a technique to coat the core/active materials, such as drug molecules or polyphenolic compounds, with a layer of polymeric materials to protect the polyphenolic moieties from several deficiencies, such as instabilities, low solubility, poor release behaviour, faster degradation, poor dissolution and absorption rate, poor bioavailability and bioaccessibility, and finally bioactivities and pharmacological responses. Different encapsulating agents protect high-value, bioactive polyphenolic compounds through physical, physicochemical, and chemical encapsulation techniques. Encapsulating agents are the polymer matrix that regulates the release of active polyphenolic compounds from the core reservoir at a constant rate, thus enhancing the bioaccessibility and bioavailability. The current review aims to profile the benefits of encapsulation for bioactive polyphenolic compounds, as well as various encapsulating agents and encapsulation techniques, to enhance the bioaccessibility and bioavailability of bioactive polyphenols.</p> Graphical abstract <p></p>