Dexlansoprazole, a proton pump inhibitor (PPI), is widely used in the treatment of gastroesophageal reflux disease (GERD) and peptic ulcers. However, its short biological half-life and pH-dependent solubility limit its therapeutic efficacy. A gastro-retentive floating drug delivery system (GRFDDS) can enhance gastric residence time, improve bioavailability, and ensure prolonged drug release. Dexlansoprazole-loaded floating tablets were prepared using hydrophilic polymers (HPMC K4M, HPMC K100M) and gas-generating agents (sodium bicarbonate, citric acid) via direct compression. A 3² factorial design was applied to optimize key formulation parameters. The prepared formulations were evaluated for pre-compression and post-compression characteristics, including hardness, swelling index, buoyancy lag time, and total floating duration. In-vitro drug release studies were performed in simulated gastric fluid (pH 1.2) for 12 hours. In vivo pharmacokinetic studies were conducted in animal models to assess bioavailability enhancement.