The present study aims to develop matrix-type buccal film therapeutic systems of Betahistine using various polymers as matrix formers. Betahistine buccal films were developed by using solvent casting technique. Various physic mechanical parameters like weight variation, thickness, folding endurance, drug content, moisture content, moisture absorption parameters. An in vitro drug release study was designed, and it was carried out using buccal film as a membrane. Results revealed that prepared films showed good physical characteristics, no drug-polymer interaction was observed. The in vitro release study revealed that F3 formulation showed maximum release in 8 hrs. The release of Betahistine appears to be dependent on polymer of the matrix. Moderately synthetic polymer matrices showed best release. The predominant release mechanism of drug through the fabricated matrices was believed to be by diffusion mechanism. Based upon the in vitro diffusion data the F3 formulation was concluded as optimized formulation.