Successful oral administration of protein drugs remains an obscure challenge. oral insulin delivery has always been a significant challenge for pharmaceutical researchers and considerable efforts are being made to deliver insulin orally. Oral insulin therapy seems to have progressed with nanotechnology research, allowing for several types of encapsulations to bypass the gastric acidic environment. Nanoparticles protect insulin against degradation and facilitate the uptake of insulin (associated or not associated to the nanoparticles) through a paracellular or a transcellular pathway. In oral insulin, the mechanism involves various nanoparticle encasings bound to insulin delivery. Continuous comparisons of in vitro and in vivo studies are essential to develop oral insulin delivery systems in near future.