Fexuprazan (DWP14012) is a novel potassium-competitive acid blocker (P-CAB) approved for the treatment of gastric acid-related diseases. The aim of this study was to develop a pharmacokinetic–pharmacodynamic (PK–PD) model of Fexuprazan to quantitatively characterize its exposure–response relationship and support effective dose prediction for gastritis treatment. A two-compartment pharmacokinetic model was developed based on plasma concentration-time profiles following oral administration of 40–80 mg in healthy subjects. The pharmacodynamic model, using an indirect response approach, described the intragastric pH modulation effect of Fexuprazan. Model parameters were estimated by fitting the observed data, and the model was successfully applied to simulate pharmacokinetic and pharmacodynamic profiles for low-dose regimens (10 mg BID and 20 mg QD), which have demonstrated clinical efficacy in Phase III trials. The developed model demonstrated high predictive accuracy and can be utilized for dose optimization and prediction of potential drug-drug interactions in future clinical studies.