Background: Mucoadhesive polymers represent a major part of site-specific and localized retention strategies in oral drug delivery. Present research was designed to synthesize and characterize a novel mucoadhesive carbohydrate polymer (thiolated gum ghatti; TGG) which was further employed to fabricate mucoadhesive tablets of domperidone using an industrially viable compression coating technique. Methods: Thiolation of gum ghatti was achieved by the ester formation (esterification) between hydroxyl group and carboxyl group of gum ghatti and thioglycolic acid. Results: TGG was characterized by various physico-chemical techniques such as FTIR, XRD, SEM and DSC techniques. In rheological studies, the observed viscosities of pure gum-mucin were 45.45 and 71.75 mPas and that of thiolated gum were 78.7 and 112.58 mPas respectively in water and simulated gastric fluid. Signifi-cant increase in viscosity for thiolated gum may be attributed to increased macromolecular interactions responsible for enhanced mucoadhesive potential of thiolated gum. In-silico studies corroborate the role of mucin gum interaction and energetic stabilization for en-hanced mucoadhesion properties of thiolated gum. Ex-vivo mucoadhesion strength of gum ghatti and thiolated gum ghatti coated tablets was found to be ranging between 4.67± 0.79 to 8.99± 0.75 g and 11.76± 1.34 to 18.83± 2.07 g respectively. Conclusion: Thiolated gum ghatti may be regarded as a promising polymer for developing different mucoadhesive drug delivery systems.