Context: Oral administration of insulin is severely limited by very low bioavailability. Biocompatible polymeric nanocarriers have been investigated to overcome this problem. Flow focusing (FF) has revolutionized current engineering of poly(D, L-lactide-co-glycolide) (PLGA) based micromedicines. This technique has never been used to formulate insulin-loaded PLGA microparticles. Objective: Investigation of the benefits rising from the synthesis of insulin-loaded PLGA microplatforms by FF, compared to double emulsion/solvent evaporation method. Materials and methods: Both synthesis methodologies were compared in terms of geometry, surface physicochemical properties and insulin vehiculization capabilities. The stability of the peptide during the formulation procedure was further analysed. Results: FF permitted the preparation of insulin-loaded microcarriers with better geometry and physicochemical properties for the oral route, along with greater insulin loading capabilities and sustained insulin release kinetics. Discussion and conclusion: Results have lead to the identification of the best formulation conditions for the engineering of insulin-loaded PLGA microparticles against diabetes.