Sesquiterpenoid peroxides are a rare group of natural metabolites isolated predominantly from various parts of plants. The biological activity of sesquiterpene peroxides has hardly been studied. This review provides information on the biological activity of 80 natural sesquiterpene peroxides. All isolated chemical compounds are divided into two groups. The first group includes sesquiterpene hydroperoxides and the second group includes sesquiterpene lactone endoperoxides. To determine the biological activity of sesquiterpene peroxides, we used the computer PASS program, which contains more than 1,000,000 natural and synthetic chemicals that exhibit more than 10,000 different activities. As shown by the analysis of these compounds, sesquiterpene peroxides are inhibitors of cell adhesion and also demonstrate antiulcer activity. In addition, individual representatives of sesquiterpene hydroperoxides showed antineoplastic and antimetastatic activity. On the other hand, sesquiterpene lactone endoperoxides demonstrated anti-inflammatory and antiprotozoal properties. The new data presented showed that sesquiterpene peroxides are an interesting group of natural medicinal preparations that can be used in pharmacology, medicine and related fields.