Abstract

Natural bioactive peptides have emerged as pivotal candidates in modern science due to their multifaceted biological activities and versatile applications across biomedicine, biotechnology, and nutraceuticals. These molecules exhibit a broad pharmacological spectrum including antimicrobial, antiplatelet, antioxidant, antihypertensive, and antitumor properties, positioning them as potent therapeutic agents and essential functional food constituents. Compared to synthetic alternatives, their inherent structural diversity, biocompatibility, and biodegradability offer a superior safety profile by minimizing systemic toxicity and adverse effects. This review provides a comprehensive analysis of the primary natural reservoirs of these peptides, which encompass terrestrial flora and fauna as well as marine organisms and microorganisms, while elucidating their complex mechanisms of action and structure-function relationships. Furthermore, we evaluate contemporary methodologies for peptide identification and optimization, such as high-throughput proteomics, computational modeling, and strategic chemical modifications aimed at enhancing metabolic stability and bioavailability. Although bottlenecks in extraction, scalable production, and proteolytic susceptibility persist, recent breakthroughs in recombinant technology and rational design are facilitating their industrial translation. Finally, we discuss future perspectives focused on the synergy between artificial intelligence, nanotechnology, and sustainable circular economy strategies to maximize the therapeutic accessibility and functional efficacy of natural peptides.