Whey Protein Hydrolysates: From Low Allergenicity to Bioactive Peptides—A Review of Advances and Challenges

Whey protein hydrolysate (WPH) has emerged as a promising functional food ingredient and nutritional supplement, owing to its enhanced digestibility, reduced allergenicity, and diverse bioactive peptides. Enzymatic hydrolysis is the primary technology for WPH production, but its industrial-scale application faces critical challenges, including bitter taste, high costs, and insufficient clinical validation. Conventional single-enzyme hydrolysis, the focus of most existing studies, is limited by low efficiency and poor peptide specificity, hindering large-scale application. Our review systematically summarizes the advantages and limitations of traditional enzymatic hydrolysis and explores emerging interdisciplinary strategies to address these bottlenecks. In particular, machine learning-based peptide prediction, bioinformatics-guided epitope screening, non-thermal processing for allergenicity reduction, and proteomics-enabled peptide identification may collectively support more rational WPH development. Integration of these approaches with enzyme engineering, real-time quality monitoring, and personalized peptide design could accelerate the emergence of intelligent and scalable production systems. By synthesizing current progress and unresolved challenges, this Review outlines a framework for advancing WPH from laboratory optimization to broader applications in functional foods, clinical nutrition, and pharmaceutical development.