Oral bioavailability is the key to the bioefficiency of food bioactive ingredients; it evaluates the relationship between foods and their health benefits. The analysis of the main factors limiting the oral bioavailability (bioaccessibility, absorption, and transformation) has led to the proposal of classification systems for pharmaceuticals and nutraceuticals (Biopharmaceuticals Classification System and Nutraceutical Bioavailability Classification Scheme). Based on the relevant studies published in the last decade, this review presents the essential aspects regarding the factors limiting the oral bioavailability of the biocomponents and different in vitro methods used to investigate the mechanisms involved in the digestion, absorption, and metabolism of biocomponents, particularly encapsulated bioactive compounds. Oral bioavailability investigated by in vitro studies provides the food and drug manufacturers with information to formulate delivery systems more efficiently and to determine the dosage of biocomponents for increase the health benefits and avoid or reduce the risk of toxicity.

Nowadays, many consumers prefer foods with a high content of nutraceuticals that contribute to the prevention or healing of chronic diseases. Therefore, in recent years, more and more researchers have studied the bioefficiency, safety, and toxicity of nutraceutical‐enriched foods. The key stage of nutraceutical bioefficiency is oral bioavailability, which involves the following processes: the release of nutraceuticals from food matrices or nanocarriers in gastrointestinal fluids, the solubilization of nutraceuticals and their interaction with other components of gastrointestinal fluids, the absorption of nutraceuticals by the epithelial layer, and the chemical and biochemical transformations into epithelial cells. These processes are endogenous factors that greatly influence the bioavailability of nutraceuticals. In addition to endogenous factors, the bioavailability of nutraceuticals is also affected by exogenous factors, such as: physicochemical properties of nutraceuticals, food matrix, food processing and storage, and so forth. Both the endogenous and exogenous factors are comprehensively analyzed in this review. Thus, the physicochemical and enzymatic processes involved in food digestion are described, highlighting the role of each stage of gastrointestinal tract (mouth, stomach, and intestine) in nutraceuticals bioaccessibility. The structure and functions of the mucus and epithelial layers, the mechanisms involved in the active and passive transport of nutraceuticals through the cell membrane, and phase I and phase II metabolism reactions are also discussed. Finally, this review focuses on several types of bioactive‐loaded nanocarriers such as lipid‐based, surfactant‐based, and biopolymeric nanocarriers that improve the bioavailability of nutraceuticals.