The species Centaurea bruguierana (DC.) Hand.-Mazz. ssp. belangerana (DC.) Bornm. (CBB) (Asteraceae), known as "Baad-Avard" in Borazjan, Bushehr Province, southern Iran, is used in folk medicine as a hypoglycemic herb in diabetes and as a remedy for peptic ulcer disorders. Total 80% EtOH extract and petroleum ether, CHCl(3), EtOAc, n-BuOH, and remaining fractions obtained by solvent-solvent fractionation of dried aerial flowering parts of the plant were investigated for anti-ulcer activity against indomethacin-induced ulcerogenesis in rats. Anti-ulcer activity was evaluated by measuring the ulcer index (UI) and ulcer inhibition. The UI was significantly reduced in all treated animals. A dramatic decrease in the UI was observed following the administration of total extract (100 mg/kg, p < 0.001) and CHCl(3) fraction (42 mg/kg, ***p < 0.001) in comparison with the control group. The percentage ulcer inhibition with total extract at a dose of 100 mg/kg (97.66%) and CHCl(3) fraction at a dose of 42 mg/kg (96.96%) was found to be higher (p < 0.001) than the reference group (cimetidine 100 mg/kg) (87.08%). The pharmacological and histological results of the present study proved that the aerial flowering parts of CBB possess preventive activity against peptic ulcer, supporting the traditional assertion in southern Iranian folk medicine.