Diabetes mellitus is a highly prevalent metabolic and chronic disease affecting millions of people in the world. The most common route of insulin therapy is the subcutaneous injection due to its low bioavailability and enzymatic degradation. The search for effective and high patient compliance insulin delivery systems has been a major challenge over many decades. The polysaccharide-based nanoparticles as delivery vehicles for insulin oral administration have recently attracted substantial interests. The present review highlights the recent advances on the development of nanoparticles prepared from polysaccharides, including chitosan, alginate, dextran and glucan, for oral delivery of insulin, overcoming multiple barriers in gastrointestinal tract. The aims of this review are first to summarize the strategies that have been applied in the past 5 years to fabricate polysaccharide-based nanoparticles for insulin oral delivery, and then to provide in-depth understanding on the mechanisms by which such nanoparticles protect insulin against degradation in the digestive tract and provide sustained release to enhance mucus permeation and transepithelial transport of insulin administered via oral route.