This review explores the in vitro and in vivo models used to study antiulcer agents, highlighting their mechanisms, efficacy, and translational challenges. Various models, including histamine H4 receptor antagonists, methylene blue-induced lesions, serotonin-induced ulcers, and ethanol-induced gastric damage, have been instrumental in understanding ulcer pathogenesis and evaluating potential therapies. In vitro assays, such as DPPH and FRAP, and in vivo studies using rodent and rabbit models, provide comprehensive insights into the antioxidant and gastroprotective effects of novel compounds. The findings demonstrate the role of oxidative stress, inflammation, and molecular pathways in ulcer development and healing. Despite the advances, limitations such as genetic variability among animal strains and differences in human gastric physiology pose challenges to the direct translation of preclinical results to clinical practice. Future research should focus on refining these models to better mimic human conditions and improve the predictive value of preclinical studies.