The human gastrointestinal tract is exposed to a variety of toxic agents, such as Helicobacter pylori (H.pylori), Nonsteroidal Anti-inflammatory Drugs (NSAIDs), gastric acid, enteric pathogenic bacteria, excessive auto immune reactions, and chronic mental stresses. These stressors generate free radicals within the gastrointestinal tissues, causing chronic inflammatory diseases, ulcers, cancers, and functional disturbances. Recent studies have demonstrated that some natural food compounds upregulate the nuclear factor erythroid 2-related factor 2- mediated antioxidant system, ameliorating or preventing these disorders. We have previously shown that dietary intake of sulforaphane-rich broccoli sprouts, ameliorates gastric inflammation induced by H. pylori, prevents NSAIDs-induced small intestinal injury, and improve functional constipation. There have been many other compounds, which enhance the nuclear factor erythroid 2-related factor 2-mediated antioxidant system, sufficient evidence for their clinical efficacy has not yet been provided. In addition, we have to pay attention to some reports, which have shown that excessive stimulation of nuclear factor erythroid 2-related factor 2 enhance chemoresistance and facilitates growth of cancer cells.