The role of the food matrix in peptide bioavailability: a review of interactions and their impact on absorption

Bioactive peptides (BAPs) derived from food proteins exhibit a wide range of health-promoting activities, but their potent in vitro bioactivity is disconnected from their often-limited efficacy in vivo. This discrepancy is driven by aggressive gastrointestinal digestion, low epithelial permeability, and rapid systemic clearance. This review assesses the critical role of the food matrix (FM) in regulating peptide bioavailability, addressing the new challenge of overcoming low oral absorption of diverse peptide classes. First, foundational concepts are established, defining the multi-scale nature of FM and the characteristics of BAPs. The physiological barriers to absorption are then detailed, focusing on enzymatic degradation and the mechanisms of transepithelial transport. The core of this review examines the specific molecular interactions between peptides and proteins, lipids, carbohydrates, and polyphenols, showing how they govern stability and bioaccessibility. A comparative analysis of dairy, plant-based, and engineered matrices illustrates how different food structures control release kinetics. Finally, methodologies from in silico prediction to in vivo models are critically evaluated. To solve these delivery challenges, we identify crucial knowledge gaps and suggest future directions, specifically advocating for matrix-engineered delivery systems (such as microencapsulation and probiotic fermentation) to establish a holistic, matrix-aware approach to functional food design. © 2026 Society of Chemical Industry.