Objective: The present study was aimed at developing Gastroretentive Bilayer drug delivery systems containing Amoxicillin Trihydrate and Ranitidine Hydrochloride for the treatment of H. pylori induced peptic ulcer to minimize the side effect, improve the prolongation of action, to reduce the frequency of drug administration. Materials and Method: The tablet is characterized by immediate release layer of Ranitidine Hydrochloride and Gastroretentive layer of Amoxicillin Trihydrate. The formulation containing Gastroretentive layer was designed using HPMC K15M and HPMC K4M as floating agents, sodium bicarbonate and citric acid as gas-generating agent. Crospovidone was used as superdisintegrant for the preparation of immediate release layer. The prepared Gastroretentive layer was evaluated for their precompression parameters, physical characteristics like hardness, friability, uniformity of weight, uniformity of drug content, swelling index, In-vitro floating studies and In-vitro drug release. For the estimation of Ranitidine Hydrochloride and Amoxicillin Trihydrate in a formulation, simultaneous estimation method was employed. Results: The release of the Ranitidine Hydrochloride from the immediate release layer was found to be 94.6% ± 0.02% in 30 minutes. The release of Amoxicillin Trihydrate for the sustained release floating layer was found to be 90.5 ± 0.06% in 12 hours. The data obtained from In-vitro release were fitted into the various kinetic models (Zero Order, Higuchi, First Order and Korsmeyer–Peppas Model). Conclusion: The best fitted model for Amoxicillin Trihydrate and Ranitidine Hydrochloride was found to be zero order release model and first order release model, respectively.