Hericium erinaceus is a culinary-medicinal mushroom that is used in traditional medicine, in folk medicine, and as medicinal cuisine in Asian countries such as China, Japan, and Korea. H. erinaceus exhibits various pharmacological properties, such as anti-cancer, immunomodulation, anti-dementia, and anti-gastric ulcer effects. The extracts of the fruiting body of H. erinaceus demonstrate anti-gastritis activity. However, the active principle in the extract, as well as the mechanism to treat gastric ulcers, remains uncertain. The current study aims to identify the active component, with anti-gastric ulcer function, from the extracts of the H. erinaceus mycelium culture. In the experiment, anti-gastric ulcer activity was evaluated using an ethanol-induced ulcer model in mice and with an 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay using MC cell lines. The results suggest that the polysaccharide fraction can significantly decrease the ulcerated area compared with the control group and the effect is fairly dose dependent, irrespective of animal or cell experiments. These results indicate that the polysaccharide fraction is the active component of the H. erinaceus mycelium culture, which protects against gastric ulcers.