The growing demand for functional and sustainable foods has driven food innovation, enhancing its nutritional value. This study aimed to develop a nutritious bread using local rye from the Trás-os-Montes region of Portugal and incorporating whey, a by-product of the dairy industry, as a replacement for water. Three bread formulations were tested: a traditional recipe with 37.5% rye flour and water (Control—CTR); the same recipe using whey instead of water (Rye Whey—RW); and a formulation with 100% local rye and whey replacing water (Full Rye Whey—FRW). Nutritional composition was assessed, including moisture, ash, protein, dietary fiber, sodium, potassium, lipids, and carbohydrates. Sensory analysis included both quantitative descriptive analysis and consumer acceptance testing. Microbiological quality was also evaluated. Whey-containing samples showed lower moisture and increased levels of ash, lipids, carbohydrates, and potassium. RW had the highest protein content (6.54 ± 0.28 g/100 g, p < 0.05), while FRW exhibited the highest dietary fiber (6.96 ± 0.15 g/100 g, p < 0.05). RW demonstrated a balanced nutritional and sensory profile, with high consumer acceptance. Overall, the combination of local rye and whey presents a promising strategy for producing nutritious bread while valorizing local agricultural resources and dairy by-products. These findings support sustainable food production practices and contribute to circular economy approaches.

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.