In the present research work mucoadhesive microspheres of Cimetidine were prepared using Ionotropic gelation technique. All the microspheres were characterized for particle size, scanning electron microscopy, FT-IR study, DSC, percentage yield, drug entrapment, stability studies and for in vitro release kinetics and found to be within the limits. Among all the formulations M12 was selected as optimized formulation based on the physicochemical and release studies. In vitro drug release study of optimized formulation M12 showed 99.12% after 12 h in a controlled manner, which is essential for anti ulcer therapy. The innovator Cimetine conventional tablet showed the drug release of 96.15% within 1 h. The drug release of Cimetidine optimized formulation M12 followed zero order and Higuchi kinetics indicating diffusion controlled drug release.