Fangmin Chen, Tong Sun, Haizhao Song
Polysaccharides are natural biopolymers with diverse bioactivities, but their clinical use in diabetes is restricted by poor solubility and bioavailability. Chemical modification provides an effective strategy to optimize polysaccharide structures, thereby enhancing their physicochemical properties and biological functions. This review summarized major chemical modification methods, focusing on introducing functional groups to sites such as hydroxyl, carboxyl, aldehyde, and amino groups. These modifications influence molecular weight distribution, monosaccharide composition, glycosidic linkage, solubility, and thermal stability, thereby modulating biological activities. Enhanced hypoglycemic effects of chemically modified polysaccharides were extensively discussed, emphasizing mechanisms such as suppression of digestive enzyme activities and the prevention of advanced glycation end-product generation, improvement of oxidative stress, improvement of gut microbiome and maintenance of gut health, and anti-inflammatory actions. This review underscored the potential of chemically modified polysaccharides as functional antidiabetic agents and advocated for further mechanistic studies and scalable, environmentally friendly modification techniques to advance their applications.