Mucoadhesive buccal tablets containing ondansetron hydrochloride (ODH) were prepared using polymers like gelatin, chitosan, xanthan gum in varying concentration of 5, 10, 15% w/w and HPMC K4M 40% w/w by direct compression technique. Precompressional studies revealed good micromeritic properties of powder blend for compression and were found as per literature limits. The prepared tablets were evaluated for thickness, hardness, uniformity of weight, drug content, friability, swelling index, mucoadhesion strength, in vitro disintegration, dissolution time and permeation studies. The formulations containing xanthan gum gave better mucoadhesion, release characteristics compared to those containing gelatin and chitosan and the rank order of mucoadhesion and permeation across sheep buccal mucosa was xanthan gum > chitosan> gelatin. The tablets apart from fulfilling all the official specifications, exhibited higher rate of release, in vitro release from all ODH buccal tablets followed Super case II transport due to polymer chain disentanglement and relaxation. and found to be stable upon conducting stability studies as per ICH guidelines at 40oC/75 % RH. The results revealed that mucoadhesive buccal tablets containing ODH were successfully formulated by direct compression technique as an alternative to conventional tablets for therapy of nausea condition in patients.