{Reference Type}: Journal Article {Title}: In vitro strategies to understand the impact of oral intake on the bioavailability and bioactivity of peptides from brewing by-products. {Author}: Ribeiro-Oliveira R;Diniz C;Ferreira IMPLVO; {Journal}: Crit Rev Food Sci Nutr {Volume}: 0 {Issue}: 0 {Year}: 2024 Jul 1 {Factor}: 11.208 {DOI}: 10.1080/10408398.2024.2362410 {Abstract}: Bioactive peptides from brewer's spent grain (BSG) and brewer's spent yeast (BSY), two by-products of the brewing industry, have great potential as functional food ingredients, dietary supplements or nutraceuticals to reduce the risk of numerous pathological conditions. Nevertheless, the oral administration of these peptides poses great challenges since peptides must undergo gastrointestinal digestion, intestinal absorption and hepatic metabolism, which can affect their bioavailability and, therefore, the expected outcomes. This review provides a comprehensive and critical analysis of the potential impact of the oral route on the bioactivity of BSG/BSY peptides as assessed by in vitro assays and identifies research gaps that require novel approaches/methodologies. The data collected indicate that in addition to the significant influence of gastrointestinal digestion, intestinal absorption and hepatic metabolism also have a major impact on the bioactivity of brewing peptides. The major gap identified was the insufficient evidence regarding hepatic metabolism, which points for the need of employing in vitro assays in this research field to provide such clarification. Thus, to reach the market, the impact of the oral route on the bioactivities of BSG/BSY peptides must be properly studied in vitro to allow adequate/effective administration (dosage/frequency) with a beneficial impact on the population health.