Citation: Aatif, M. Current Understanding of Polyphenols to Enhance Bioavailability for Better Therapies. Biomedicines 2023, 11, 2078. https://doi.org/10.3390/ biomedicines11072078 Academic Editors: Fernando de Carvalho da Silva, Bruno Kaufmann Robbs and Gabriela Nestal De Moraes Received: 27 May 2023 Revised: 25 June 2023 Accepted: 4 July 2023 Published: 24 July 2023 Copyright: © 2023 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). biomedicines Review Current Understanding of Polyphenols to Enhance Bioavailability for Better Therapies Mohammad Aatif Department of Public Health, College of Applied Medical Sciences, King Faisal University, Al Ahsa 31982, Saudi Arabia; maahmad@kfu.edu.sa Abstract: In recent years, plant polyphenols have become a popular focus for the development of novel functional foods. Polyphenols, a class of bioactive compounds, including flavonoids, phenolic acids, and lignans, are commonly found in plant-based diets with a variety of biological actions, including antioxidant, anti-inflammatory, and anticancer effects. Unfortunately, polyphenols are not widely used in nutraceuticals since many of the chemicals in polyphenols possess poor oral bioavailability. Thankfully, polyphenols can be encapsulated and transported using bio-based nanocarriers, thereby increasing their bioavailability. Polyphenols’ limited water solubility and low bioavailability are limiting factors for their practical usage, but this issue can be resolved if suitable delivery vehicles are developed for encapsulating and delivering polyphenolic compounds. This paper provides an overview of the study of nanocarriers for the enhancement of polyphenol oral bioavailability, as well as a summary of the health advantages of polyphenols in the prevention and treatment of several diseases. Keywords: polyphenols; bioavailability; nanocarriers; molecular mechanisms; human health 1. Introduction The health benefits of plant-based functional foods have attracted a growing amount of scientific interest, and plant polyphenols, one of the most common chemical components of plants, have particular attention. A diet full of vegetables, fruits, grains, tea, and coffee contains polyphenols in their natural forms. Polyphenolic compounds have a wide range of varied structures based on phenolic rings [1,2] and can be broken down into phenolic acids, flavonoids, anthocyanins, and tannins. Several foods consist of bioactive chemicals or molecules that have a biological effect on the body. Polyphenols are one type of bioactive compound found in plant diets [2,3]. Some polyphenols can be obtained through reprocessing natural substances, while others can be separated and extracted straight from natural foods. The chemical composition of polyphenols determines their rate of absorption and the extent of their action in the digestive tract [4]. Because of their unique chemical composition, polyphenols can serve as effective preventative agents against chronic and degenerative diseases [3–5]. The protective effects of polyphenols against cardiovascular disease, neurological disease, liver disease, diabetes, and cancer have been demonstrated by a number of researchers [6–12]. Polyphenols have been shown in multiple research to be helpful to intestinal health and to have beneficial properties, such as lowering inflammation and protecting against cancer through controlling the gut flora [2,13]. This is why they are frequently included in functional diet menus, which aim to provide health benefits through ingestion. As the global population grows and the awareness of the need to maintain a healthy lifestyle expands, so does the demand for polyphenols in the market. The use of polyphenols in nutraceuticals is hindered, however, because many polyphenolic substances have poor oral bioavailability. Biomedicines 2023, 11, 2078. https://doi.org/10.3390/biomedicines11072078 https://www.mdpi.com/journal/biomedicines