Helicobacter pylori infection, which is the main cause of gastritis, peptic ulcer disease and gastric cancer, is associated with infiltration of the gastric mucosa by neutrophils, macrophages, and B and T lymphocytes. However, this immune and inflammatory response cannot completely control the bacterial infection, and leaves the host prone to complications resulting from persistent inflammation. As a result, H. pylori infection may cause chronic inflammation, accumulation of reactive oxygen species, and oxidative DNA damage in the gastric mucosa. The H. pylori bacterial effector proteins are transported into the gastric host cells via the type IV secretory system, and regulate intracellular signal transduction. This mechanism provides novel insight into how H. pylori survives in the acidic environment of the human stomach. In cases with persistent gastric infection, the chronic gastritis may remain asymptomatic or may evolve into more severe diseases, such as peptic ulcer disease and chronic atrophic gastritis. In addition, infection with H. pylori increases the risk of development of gastric cancer and mucosa-associated lymphoid tissue lymphoma. This review focuses on the oxidative mechanisms involved in the bacterial and host-mucosal responses during colonization of the gastric mucosa by H. pylori.