Objective: The aim of the present study was to formulate and evaluate novel gastroretentive in-situ gel of Roxatidine acetate for the treatment of gastric ulcer disease. Methods: A gastroretentive in-situ gel of Roxatidine acetate was formulated by natural polymer using different concentrations of chitosan and vigna mungo gum as gelling agent. The compatibility study was done by DSC and FTIR. The prepared formulations of in-situ gel were evaluated with various parameter like gelling capacity, viscosity, pH, drug content, gel strength, floating ability, gel density, water uptake, in-vitro drug release and stability studies. Results: Selected S4 and G4 gastroretentive in-situ gel of Roxatidine acetate formulations were found to be best on the basis of results of evaluation parameters. The S4 & G4 drug release rate was retained up to 12 hours. The rises in concentrations of gelling agent decrease the rate of drug release. It is indicated that prepared formulation exhibited controlled release of drug at prolonged time. The release rate of drug from the formulation surface was found to be best fit Korsmeyer-Peppas model model for S4 & G4 (R2=0.9956, n value=0.3699; R2=0.9984, n value=0.3767; ) and were implies that the optimised formulations patterns of release preceded by Fickian diffusion. The stability of Roxatidine acetate optimised formulations S4 & G4 showed no changes in physical appearance, drug content, dissolution profile and HPLC chromatograms. The evaluation parameter and results revealed that Roxatidine acetate gastroretentive in-situ gel formulation was found to be stable at 40oC/75 percent RH for three months. Conclusion: The development of a once daily dosage, from in situ gel prepared S4 & G4 formulation can able to provide prolonged drug release, improve the bioavailability of the drug, and increase patient compliance. The result of evaluation revealed that S4 & G4 formulation can improve therapeutic action for the treatment of gastric ulcer disease