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The drug delivery systems (DDS) are interdisciplinary approaches that combine polymer science, pharmaceutics, bioconjugate chemistry, and molecular biology. Till recent, injections remained the most common means for administering therapeutic proteins and peptides such as insulin, because of their poor oral bioavailability. Designing and formulating a polypeptide drug delivery has been a persistent challenge because of their unfavorable physicochemical properties, which includes enzymatic degradation, poor membrane permeability and large molecular size. Due to the inconvenience of insulin injections, various approaches have been attempted to formulate insulin for administration by non-injectable routes. Various strategies currently under investigation include chemical modification, formulation vehicles and use of enzyme inhibitors, absorption enhancers and mucoadhesive polymers. To minimize drug degradation and loss, to prevent harmful side-effects and to increase drug bioavailability and the fraction of the drug accumulated in the required zone, various drug delivery and drug targeting systems are currently under development. Among drug carriers one can name soluble polymers, microparticles made of insoluble or biodegradable natural and synthetic polymers, microcapsules, lipoproteins, liposomes, gelfoams, niosomes and micelles. Different approaches to deliver insulin including transdermal, transmucosal, pulmonary route using dry aerosols and inhalers, smart hydrogels, nasal delivery and oral delivery has resulted in recent developments in treatment of diabetes. This review summarizes different pharmaceutical approaches which overcome various physiological barriers that help to improve bioavailability that ultimately achieve formulation goals for insulin delivery by a patient-friendly route.