Bo Zheng, Yihan Hu, Guo Saiqin, Bin Zheng, Xingwei Xiang
Aquatic-derived peptides (ADPs) are bioactive peptides from fish, shellfish, algae, and aquatic by-products. Reported biochemical activities include antioxidant, ACE-inhibitory, and mineral-binding properties, with immunomodulatory and metabolic functions reported. However, an integrated understanding linking peptide structure, bioavailability, and systemic functions remains incomplete. This review summarizes advances from 2020 to 2026 across in silico, in vitro, animal, and human studies, integrating peptidomics, molecular simulations, transport biology, and multi-omics. Particular attention is given to potential pathways through which ADPs may influence the gut-brain, gut-liver, gut-bone, and gut-skin axes. Emerging delivery strategies, including nanoencapsulation, hydrogel-based carriers, and targeted-release systems, are discussed for peptide stability and gastrointestinal delivery. Finally, we summarize challenges in structural standardization, human mechanistic validation, and regulatory considerations, and discuss future directions including AI-assisted peptide design and precision nutrition. Overall, current evidence supports sequence-dependent bioactivity and selected digestive and transport effects, whereas causal multi-organ and individualized responses remain insufficiently validated in humans.