Over the last few decades, various natural polymers have been applied to the problem of oral insulin delivery using advanced nanotechnology. Parenteral administration of insulin is widely accepted, but administration via the oral route could overcome the poor patient compliance with repeated injection. Polymers from natural as well as synthetic sources have recently been used in the synthesis of insulin delivery vehicles suitable for oral administration. The biopolymer chitosan has been widely studied in oral insulin delivery due to its favorable properties such as biocompatibility, biodegradability, non-immunogenicity and non-toxicity. This review focuses on progress in the synthesis of chitosan and modified chitosan nanoparticles for efficient oral insulin delivery, with an emphasis on the biological efficacy of the nanoparticles. Obstacles to oral delivery and possible remedies are also brought into focus. Modifications to protect insulin from the harsh acidic environment of the gastro-intestinal (GI) tract are described. Chemical barriers such as the acidic gastric pH and the presence of proteolytic enzymes in the stomach and intestine limit the effective absorption of external insulin within the GI tract. Absorption of insulin is physically hindered by the absorption barrier consisting of a single layer of columnar epithelial cells joined at the apical surface by a tight junction complex. The presence of negative charges in the junction complex leads to segregation of the apical layer from the basolateral compartment of the epithelial cells, making the intestinal environment selective for particles based on size and charge. Nanoparticles are able to overcome these barriers and deliver insulin. While this technology still has some drawbacks, chitosan and modified chitosan nanoparticles are highly promising agents for oral insulin delivery. © 2012 Elsevier Ltd.