Folkloric medicines such as Chinese herbal medicine and Ayurveda, have proven efficacy backed by a long history. Mitragyna speciosa, which belongs to the Rubiaceae family, is endemic to the tropics of Southeast Asia, where it is called “Kratom” in Thailand and “Biak Biak” in Malaysia. Traditionally, the leaf of this plant has been used to alleviate the fatigue of workers laboring in the scorching heat and as a substitute for opium. Many chemists have been fascinated by its special biological activity, and isolation and structure elucidation studies of this plant have been conducted since the 1960s. As a result, several monoterpenoid indole alkaloids have been found. Our group also studied the constituents of this plant and found that 7-hydroxymitragynine, a minor component, has potent analgesic activity mediated by opioid μ-receptors. In this talk, we will show that we artificially supplied 7-hydroxymitragynine by organic synthesis (total synthesis) and subsequently found its derivatives with potent analgesic activity through structure-activity relationship studies. We also found that these Mitragyna alkaloids are G protein-biased agonists of the opioid μ-receptor.