Objectives: The present investigation is concerned with formulation and evaluation of mucoadhesive buccal tablets containing antidiabetic drug, glimepiride, to circumvent the first pass effect and to improve its bioavailability with reduction in dosing frequency and dose related side effects. Methods: The tablets were prepared by direct compression method. The tablets were tested for weight variation, hardness, surface pH, drug content uniformity, percentage swelling index, bio adhesive strength, exvivo residence time in-vitro drug dissolution study, in-vitro drug release kinetic study, ex-vivo permeation study and stability study. Results: FTIR studies showed no evidence on interactions between drug, polymers, and excipients. The surface pH, bio adhesive strength, ex-vivo residence timeand swelling index of formulation was found to be 6.80±0.02, 36.3±0.04g, 325min and 289.8±0.52%, respectively. The formulation containing 4 mg of glimepiride exhibited 6 h sustained drug release i.e. 93.98±0.8% with desired therapeutic concentration. The drug permeation from the formulation was slow and steady and 3.56 mg of glimepiride could permeate through sheep buccal membrane with a flux of 0.27 mg hr-1 cm-2 . The in-vitro release kinetics studies reveal that all formulations fits well with zero order kinetics and followed non-Fickian diffusion mechanism. Conclusion: Hence, it was concluded that the best formulation was suitable for all the evaluation parameters and can be permeated through human buccal mucosa.