Diabetes Mellitus (DM) is a type of chronic metabolic disease that has affected millions of people worldwide. DM is known with a defect in the amount of insulin secretion, insulin functions, or both. This deficiency leads to an increase in the amounts of glucose, which could be accompanied by long-term multiple organ damages such as eyes, kidneys, heart, and nervous system. Thus, introducing an appropriate approach for diagnosis and treatment of different types of DM is the challenge of researches in this era. Nanomedicine is the effective alternative in this purpose. Different types of polymeric nanoparticles (PNPs) are one of the most important classes of nanoparticles, for diabetic management. Different types of PNPs, in two forms of natural and synthetic polymers with different properties are new methods for DM treatment and diagnosis. The transport mechanisms of these types of nano-carriers across the epithelium, via paracellular and transcellular pathways play a vital role in their mode of action. Finally, the clinical use of PNPs in the treatment and diagnosis of DM is a purposeful area in DM management. PNPs will be considered one of the most promising methods for DM management.