Our study evaluated the effect of Chrysanthemum coronarium L. (CC) leaves on ethanol-induced acute gastric ulcers in Wistar rats. Materials and Methods: The organic extract of CC was obtained by Soxhlet extraction with methanol and then divided into two dose groups: 250 mg/kg and 500 mg/kg. Omeprazole was used as a positive control at 20 mg/ kg. Our extract was subjected to the separation of bioactive compounds by High-Performance Liquid Chromatography (HPLC). Lethality tests (LD50) were carried out using standard procedures. Gastric protection was assessed by measuring gastric juice volume, total acidity, and free acidity. Gastric mucosal damage was assessed by histopathological examination. Results: Chromatographic analysis of the Methanolic Extract of Chrysanthemum coronarium L. (MECC) identified the presence of 19 phenolic compounds, representing 46.47% of the total sample. The dominant components were o-coumaric acid (9.55%), chlorogenic acid (6%), myricetin (4.19%), and benzoic acid (2.87%). Oral LD50 value was more than 5000 mg/kg in rat. In the present study, the methanolic extract of CC decreased total and free gastric acidity (53.80±7.038 and 17.8±2.375 respectively) for the 500 mg/kg dose and (60.40±4.490 and 24.8±1.855 respectively) for the 250 mg/kg dose. Omeprazole also decreased free and total gastric acidity (54.40±3.092 and 20±2.449 respectively), compared with the ethanol groups (19.40±2.909 and 4.4±0.678 respectively). In the histological study, we found that the gastric mucosal barrier could be significantly strengthened when the rats were pretreated with 500 mg/kg of the MECC and showed almost normal histology compared with the ethanol-ulcerated groups. Conclusion: Based on the present results, we can conclude that CC leaves could be a promising food for the protection of the gastric mucosa against ethanol-induced lesions