ABSTRACT: There is an increased interest in the role that some nutrients may play in preventing or ameliorating the effect of major diseases (for example, some types of cancer, cardiovascular diseases, eye disorders, among others). In this respect, the bioavailability or the proportion of an ingested nutrient that is made available (that is, delivered to the bloodstream) for its intended mode of action is more relevant than the total amount present in the original food. Disruption of the natural matrix or the microstructure created during processing may influence the release, transformation, and subsequent absorption of some nutrients in the digestive tract. Alternatively, extracts of bioactive molecules (for example, nutraceuticals) and beneficial microorganisms may be protected during their transit in the digestive system to the absorption sites by encapsulation in designed matrices. This review summarizes relevant in vivo and in vitro methods used to assess the bioavailability of some nutrients (mostly phytochemicals), types of microstructural changes imparted by processing and during food ingestion that are relevant in matrix-nutrient interactions, and their effect on the bioavailability of selected nutrients.