Abstract
Cheese whey, a low-value by-product of cheese production, has gained renewed attention within the transition toward sustainable and circular food systems. Despite posing environmental challenges due to its high biochemical and chemical oxygen demand, whey retains a substantial proportion of milk nutrients, notably high-quality proteins that can be converted into bioactive peptides with potential health benefits. These peptides have been shown to modulate key biological pathways, including angiotensin-converting enzyme inhibition, nitric oxide bioavailability, oxidative stress balance, and inflammatory signaling, providing mechanistic plausibility for cardioprotective and immunomodulatory effects. However, the translation of promising in vitro and animal findings into consistent human health outcomes remains constrained by variability in peptide composition, processing conditions, bioavailability, and study design. This narrative review critically synthesizes current evidence on the functional properties of whey-derived peptides, with particular emphasis on cardiovascular and immunomodulatory outcomes across experimental models. In addition, the review situates whey upcycling within the Portuguese agro-food context, highlighting regional cheese production as both an environmental challenge and an opportunity for sustainable innovation. By integrating mechanistic evidence with sustainability-driven valorization strategies, this review aims to clarify the translational potential of whey-derived peptides as functional food ingredients.