Delivery of drugs into or via the oral cavity offers some distinct advantages due to the easy access to the oral mucosa, fast onset of action, and avoidance of hepatic and intestinal degradation mechanisms. To overcome the effective removal mechanisms existing in this area, bioadhesive drug delivery systems are considered a promising approach as they facilitate a close contact between the drug and the oral mucosa. In this study, bioadhesive chitosan-based microparticles of metformin hydrochloride were prepared by spray drying aqueous dispersions with different chitosan:metformin ratios and chitosan grades with increasing molecular weights. A recently developed ex vivo flow retention model with porcine buccal mucosa was used to evaluate the bioadhesive properties of spray dried microparticles. An important outcome of this study was that microparticles with the desired metformin content could be prepared and analyzed using the ex vivo retention model. We observed an increase in metformin retention on porcine mucosa with increasing chitosan:metformin ratios, while no effect of increasing the chitosan molecular weight was found. Rheological characterization of feeds for spray drying was performed and used for designing the microparticles. This way, novel microparticles with similar particle size distribution, high encapsulation efficiencies, and low moisture content were obtained independent of the chitosan:metformin ratio and the chitosan molecular weight. In conclusion, chitosan:metformin microparticles with significant bioadhesive properties on porcine buccal mucosa were developed.