The current study aimed to formulate gelatin/sodium alginate nanoparticles utilizing BÜCHI nano spray dryer B-90. Nanoparticles possess many of the advantages including new routes of drug administrations and sustained release properties. Utilizing B-90 technology, metformin hydrochloride (MET) nanoparticles were successfully developed. Preformulation studies such as atomization head mesh size, flow rate, head temperature, polymer viscosity, and surface tension, were adjusted. Additionally, post-formulation characters such as particle size, flowability, surface scan, and dissolution profiles, were evaluated. Spray head (7 µm hole), a flow rate (3.5 mL/min) and head temperature (120 °C) were optimized. Polymer viscosity was less than 11.2 cP with a surface tension less than 70.1 dyne/cm. Moreover, anti-diabetic effects of MET formulations were evaluated in streptozotocin-induced diabetic rats. Here, discrete, non-aggregated free flowing nanoparticle powders with a particle size less than 850 nm were generated. Gelatin/sodium-alginate (1:3) produced nanoparticles were successfully sustained the in vitro release profile of the drug. In vivo evaluations of the previous formula showed a significant reduction of blood glucose level over 24 h. In conclusion, Nano Spray Dryer B–90 (Büchi Labortechnik AG) offers a promising technology for nanoparticles formulation as controlled drug delivery systems enhancing compliance of type-II diabetic patients.