Lichens are symbiotic relationship between fungi and algae or cyanobacteria. Secondary metabolites from lichens are known as lichen substances. We investigated depsidone and depside from lichens 1-6 in the context of their action to prevent gastric ulcer on the model of HCl/ethanol in mice for the first time. Doses of 30 mg/kg of lichen substances 1-6 and positive control (lansoprazole) significantly diminished the lesion index compared with negative control (treated only with HCl/EtOH). Lobaric acid 1, atranorin 2 and psoromic acid 5 reduced the gastric lesions by 76%, 63% and 65%, while for variolaric acid 3, diffractaic acid 4 and perlatolic acid 6 their values were 32%, 14% and 45%, respectively. Our results suggest that lichens have potential as a suite of gastroprotective molecules.