This chapter portrays various advancements related to the non-invasive delivery of the anti-diabetics via polysaccharide nanoparticle delivery systems. In oral drug delivery, nanotechnologies are helpful in the transcytosis of drugs through the tight epithelial barrier, in the delivery of poorly hydrophilic drugs, in the targeted drug delivery to a desired site in the gastrointestinal tract and the transcellular and intracellular delivery of the drugs. To achieve more advantages from the nanoparticular drug delivery system, polymeric nanoparticular formulation has been a great approach in the oral delivery of macromolecules, like insulin. The chapter discusses the characteristics of polysaccharides, including solubility, biocompatibility, biodegradability, and the potentiality for modification of several polysaccharides, which makes them important for being used in drug delivery systems. Polysaccharidic nanoparticles are being used as a promising approach in the oral delivery of insulin and other anti-diabetic drugs. This drug delivery system also provides protection of active ingredient from abrasive gastrointestinal environment and sustained/controlled released properties.