Objective: Gastro retentive drug delivery system (GRDDS) pertaining to its attributes like gastric retention time and the extended drug release profile has significantly improved patient compliance. The objective of the present study was to formulate and evaluate a stomach-specific floating-bioadhesive tablets (FBTs) of imatinib mesylate (IM) for prolonged residence in the stomach in the treatment of gastrointestinal stromal tumours (GIST). Methods:All the FBTs were prepared with hydroxypropyl methyl cellulose (HPMC) K 15M, guar gum, sodium alginate, and carbopol 971P using direct compression technique. Physical characterization, in vitro dissolution, swelling characteristics, the mucoadhesive force along with data analysis was done for each FBT. Results:The pre-compression characteristics of powder mixtures found to be satisfactory for all formulation batches. The results of physical evaluation for all batches were complying with pharmacopoeia specification. The swelling index for all formulation batches was approximately 100% after 8 h. The bioadhesive force (mean±SD) reported in a range of 0.05±0.09 to 0.18±0.06 N/m 2 Conclusion: Formulation batch IB9 reported a considerable swelling index, floating behaviour, more bioadhesive strength with uniform drug release pattern. Therefore formulation batch IB9 was selected as optimized batch and kept for further evaluation studies.. It was observed that the release rate of FBTs was decreased with an increment of viscosity and concentration of the polymer. Formulation batches IB1, IB2, IB4, IB5, IB6, IB9, IB10, IB11, and IB13 follows Higuchi Matrix model kinetics; whereas IB3, IB7, IB8, and IB12 follows Korsmeyer-Peppas model kinetics.