Chitosan's toxicity to the gastrointestinal tract is an impediment to its use as an insulin carrier. While chitosan unlocks tight connections, hazardous chemicals can easily enter the bloodstream via the paracellular route. On the other hand, excessive positive charges are trapped in the mucus layer and cannot enter the circulation. To combat retention, several negatively charged polymers, such as alginate nano compounds and polyglutamic acid compounds, have been employed to alter chitosan nanoparticles, increasing permeability across the mucus layer and oral bioavailability. A variety of insulin nanocarriers, including chitosan, have recently completed clinical studies , most of which failed. They have drawbacks such as toxicity, limited oral bioavailability, and an increase in intraindividual insulin absorption differences. Biocompatibility, biodegradability, and immunological reactions should be taken into account in the near future for developing clinically meaningful insulin-loaded chitosan nanocarriers. As a result, several factors must be considered while developing innovative insulin nanocarriers, like those from chitosan derivatives. Some of the characteristics include the optimal particle size for interaction with the intestinal mucosa, the stability of the nanocarriers in biological fluids following in vivo administration, surface chemical composition, internal chemical composition, and the use of targeting ligands specific to apical membrane receptors.