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The objective of the present study was to study physicochemical properties of mucoadhesive microspheres of metronidazole to develop sustained release formulation for the treatment of periodontal diseases. The prepared microspheres would characterize to remains at affected area for longer duration pertaining to mucoadhesive property of formulation. We prepared mucoadhesive microspheres for metronidazole in six batches (i.e. F1-F6) using Xanthan gum (Xn) and Sodium CMC (Na-CMC) in different drug polymer ratios by adopting solvent evaporation method. The drug-polymer and excipient compatibility was determined by IR- spectrophotometric analysis and there was not any chemical or physical interaction observed between drug & polymer. All prepared formulations were subjected to evaluate physicochemical studies such as % yield, particle size, drug entrapment efficiency, surface morphology, mucoadhesive test, swelling index, in-vitro drug release, release kinetics and stability studies. The results analysis was found that the adopted method for the formulation of designed schemes was reproducible and easy to work on it. All the comparative results were found innovative and satisfactory. In-vitro release studies indicated that the metformin loaded mucoadhesive microspheres provided controlled drug release over a period of 12 hrs. The optimized batch no.-F6 showed percentage yield (87.95%), particle size (200.51µm), Entrapment efficiency (78.36 ± 0.028%), and swelling index (84.22%) with good mucoadhesive strength. Percent drug release in pH 6.8 phosphate buffer was found to be 90.936 ± 0.190%. So that the present studied revealed that the mucoadhesive microspheres using this particular method is useful and novice and also impetus to other researchers in designing this formulation using other drugs in improvising drug therapy for oral cavity. [ABSTRACT FROM AUTHOR]