Polysaccharides represent a structurally diverse class of natural macromolecules with broad biomedical potential. Recent advances in extraction technologies, structural characterization, chemical modification and multi-omics have substantially deepened current understanding of their structural complexity and the determinants of biological activity. This review first summarizes methodological developments in extraction, fractionation and fine-structure elucidation, and then discusses how chemical modification strategies expand the functional space of natural polysaccharides by enhancing solubility, stability and target engagement. On this basis, we integrate mechanistic evidence across several major application domains, including glycolipid metabolism regulation, protection against liver injury, intervention in intestinal inflammation and cancer immunotherapy. Particular emphasis is placed on the multi-target and microenvironment-responsive properties of polysaccharides, involving coordinated modulation of metabolic, oxidative, inflammatory and immune pathways as well as gut microbiota dependent networks. Finally, we outline the current landscape of clinical and translational applications of polysaccharide-based therapeutics, biomaterials and functional foods, and briefly highlight key issues related to structural heterogeneity, standardization and in vivo fate that still need to be addressed. Integrated research frameworks that couple (1) high-resolution structural analysis, (2) multi-scale mechanistic investigation, (3) multi-omics profiling and (4) artificial intelligence-assisted data integration are expected to clarify polysaccharide structure function relationships and to further support rational design and clinical translation.
Cao et al. (2026) studied this question.