Polysaccharides are biopolymers distinguished by their complex secondary structures executing various roles in microorganisms, plants, and animals. They are made up of long monomers of similar type or as a combination of other monomeric chains. Polysaccharides are considered superior as compared to other polymers due to their diversity in charge and size, biodegradability, abundance, bio-compatibility, and less toxicity. These natural polymers are widely used in designing of nanoparticles (NPs) which possess wide applications in therapeutics, diagnostics, delivery and protection of bioactive compounds or drugs. The side chain reactive groups of polysaccharides are advantageous for functionalization with nanoparticle-based conjugates or therapeutic agents such as small molecules, proteins, peptides and nucleic acids. Polysaccharide NPs show excellent pharmacokinetic and drug delivery properties, facilitate improved oral absorption, control the release of drugs, increases in vivo retention capability, targeted delivery, and exert synergistic effects. This review updates the usage of polysaccharides based NPs particularly cellulose, chitosan, hyaluronic acid, alginate, dextran, starch, cyclodextrins, pullulan, and their combinations with promising applications in diabetes, organ fibrosis and arthritis. © 2021 Elsevier Ltd