Helicobacter pylori is a major cause of chronic gastritis, peptic ulcers, and gastric cancer, yet its eradication is increasingly challenged by antibiotic resistance and poor drug retention in the gastric mucosa. In this study, we developed and characterized iodine-incorporated chitosan-coated starch nanoparticle (I-CS-SNP) as a dual-responsive antibacterial platform. The nanoparticles exhibited uniform size, high iodine loading, and strong mucoadhesive properties with mucopenetrative capability. Iodine release was triggered by mucin interactions and bacterial adhesion, leading to effective H. pylori eradication through biofilm disruption and membrane damage. Antibacterial assessments confirmed significant bactericidal activity, while cytotoxicity assays demonstrated excellent biocompatibility with Caco-2 cells. Additionally, I-CS-SNP maintained stability in simulated gastric conditions, ensuring controlled iodine delivery. The results of this study demonstrate I-CS-SNP as a promising alternative to conventional antibiotics, providing targeted, sustained antibacterial action while preserving mucosal integrity.