SummaryThe discussions around biopeptides generated from foods are associated with the numerous physiologic functions and therapeutic interventions that they potentiate, especially toward cardiovascular and degenerative diseases. The recurring issue about these biopeptides, however, is the wide gap left between laboratory experimentations and human intervention studies, apart from the fact that the conditions of testing or validation are not the same in both instances. Therefore, the gastrointestinal processing of biopeptides must be on par with their bioaccessibility, which is a critical step toward their bioavailability. The checks and balances of bioaccessibility are associated with the effects of the gastrointestinal enzymes, the interplay of other micro‐ and macro‐nutrients in whole or part, as well as the disruption of the integrity of the intestinal mucosal cells. We herein discussed the interplay of biopeptides with food matrices with regard to metal‐, phenol‐, lipid‐, and sugar‐peptide complexes, including mucins and other gastrointestinal enzyme secretion. These most common parameters and mechanistic activities led to the proposition of novel techniques for ensuring peptides' bioaccessibility and physiologic functions, a backdrop for futuristic studies that would contribute to our understanding and actualisation of bioaccessible peptides well incorporated and maintained in desirable functional food products.