Inflammation and oxidative stress are two aspects of the pathology of many diseases, and they also promote each other, causing a vicious cycle of the disease. Hydrogen-rich water is the water rich in hydrogen. Studies have proved that hydrogen-rich water can selectively reduce hydroxyl radicals and ameliorate oxidative and inflammatory injuries to organs and tissues under different pathological conditions. In recent years, it has been found that hydrogen-rich water can improve the inflammatory conditions of rheumatoid arthritis, colitis, hepatitis, pancreatitis, etc. Its anti-inflammatory effects are related to the amelioration of oxidative stress and regulation of the signal transduction pathways such as p38-mitogen-activated protein kinase (p38-MAPK) and nuclear factor κB (NF-κB). In the present review, the anti-inflammatory activity of hydrogen-rich water and its molecular mechanisms are summarized and discussed.