The purpose of this study was to evaluate the in vivo floating behaviour of levofloxacin floating tablets that had been produced using an experimental design approach for the purpose of treating an infection caused by Helicobacter pylori. A three-factor, three-level Box-Behnken design was employed in the formulation of the floating tablets. The, HPMC K100M content, and HPMC K4M content and the Xanthan gum content were employed as the independent variables in this model. The optimized formulation exhibited desirable in vitro characteristics, including a high swelling index and prolonged drug release. In the in vivo investigation using rabbits, X-ray imaging demonstrated the gastric retention of the levofloxacin floating tablets over a period exceeding 12 hours. The tablets remained buoyant in the upper portion of the stomach, indicating their sustained floating behaviour. These findings highlight the potential of the developed levofloxacin floating tablets as an effective drug delivery system for H. pylori eradication, offering prolonged gastric retention and improved therapeutic outcomes