Purpose <p>Oral conventional drug delivery systems for the treatment of <i>H. pylori</i> infection often fail to address challenges including limited gastric retention time, inadequate drug release, and the need for frequent dosing.</p> Methods <p>Gastro retentive floating tablets were formulated for the first time with the active drug ingredient and the polymers, HPMC100 (hydroxypropyl-methylcellulose), MCC (microcrystalline cellulose), sodium alginate, chitosan, and carbopol 974P. The objective of the current study was to develop gastro retentive-floating tablets to sustain drug substances in the stomach to improve the prolonged drug retention, oral bioavailability, and site-specific action in the stomach region. The direct compression method was used to fabricate the floating tablets.</p> Results <p>The quality control test of the prepared tablets fell within the USP standard limits. The tablets prolonged the drug release rates for up to 12&#xa0;h. Tablets showed satisfactory swelling behavior, which ranged from 60 ± 0.11 to 66 ± 0.14%, and their density was lower than pure water (1.004&#xa0;g/cm³). According to the buoyancy study, the floating lag time (68 ± 0.07) and total floating time (&gt; 12) showed excellent floating behavior. The results of the kinetic model showed that the release of drug from floating gastroretentive tablets followed an anomalous or non-Fickian diffusion kinetic model. The dissolution study showed that the formulated gastroretentive floating tablets have the levofloxacin hemihydrate ability to provide an extended release effect and prolong the half-life of levofloxacin in the stomach.</p> Conclusion <p>the current study showed that the gastroretentive floating tablets have promise for gastroretentive drug administration at the site of absorption, resulting in enhanced drug bioavailability and improved therapy outcomes and patient compliance.</p>