Venlafaxine is a serotonin norepinephrine reuptake inhibitor used for treating depression. Due to extensive first pass metabolism, its oral bioavailability is around 45%. The aim of the present study is to develop and evaluate buccoadhesive tablets of venlafaxine using natural resins like olibanum and colophony as mucoadhesive release retarding agents with an objective to bypass first-pass effect, to improve the bioavailability of the drug, to minimize the dose dependent side effects as well as to improve patient compliance. Buccoadhesive tablets were prepared by wet granulation technique and ethyl cellulose employed as a backing laminate for the preparation of unidirectional drug release of buccoadhesive tablets. The prepared granules of different batches were of good flow properties. The physicochemical interactions for pure drug and optimized formulation were investigated by Infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. The formulation F9 was found to be the optimized formulation based on drug dissolution studies. Mucoadhesive properties of resins employed were increased with increase in the concentration of polymer which was proved from ex-vivo residence time and detachment force measurement. The drug release was found to be following Fickian diffusion. It was concluded that resin based buccoadhesive tablets of venlafaxine exhibiting good controlled release characteristics and were proved as efficient mucoadhesive agents.