Peptic ulcer disease, affecting almost 20% of the worldwide population, depicts an urgent need for effective treatment due to the limited therapeutic options available and the side effects associated with current drugs. The disease is often linked with Helicobacter pylori infection and NSAID usage, both of which compromise the mucosal lining of the stomach. There is growing evidence that dietary polyphenols can contribute to the prevention and management of various chronic diseases, including cancer and gastrointestinal disorders. Among these, green tea has garnered significant attention due to its rich polyphenolic content and associated health benefits. The abundance of green tea polyphenols (GTPs) exhibits chemoprotective, antimicrobial, and antioxidant properties. This study explores a set of 65 GTPs against penicillin-binding proteins (PBPs) as a molecular target to prevent peptic ulceration. Our molecular docking analysis revealed that the polyphenol ‘Epigallocatechin gallate’ (EGCG) exhibited effective binding affinity towards PBPs (PDB code: 1QMF) with a docking score of -11.23 kcal/mol. Additionally, theaflavin-3-gallate and epigallocatechin also showed strong docking scores. In-silico ADME profiling indicated favorable pharmacokinetics for EGCG, including no AMES toxicity, low hERG inhibition, and good intestinal absorption. Our study highlights EGCG as a potential inhibitor of H. pylori, providing a promising natural therapeutic candidate for the management of peptic ulcer disease.