Ayahuasca is a psychoactive plant mixture used in ceremonial contexts throughout Western Amazonia. Its use has expanded globally in recent decades and become popular among westerners who travel to the Peruvian Amazon in increasing numbers to experience its reportedly healing effects. Through a review of relevant literature on Amazonian shamanism, combined with the authors’ ethnographic data from shamanic tourism contexts of the Peruvian Amazon and neo-shamanic networks in Australia (collected between 2003 and 2015 – with a total of 227 people interviewed or surveyed, including healers and participants), we demonstrate that purging has been integral to the therapeutic use of ayahuasca across and beyond Amazonia. Therapeutic approaches to ayahuasca point to combined modulations of the gut and the mind, and the bodily and the social, that are expressed through discourse about healing and the body. Relating ethnographic evidence to recent scientific studies that connect the gut to emotional health, we do not approach the gut as merely biological ground on which cultural meanings are imposed, but rather as simultaneously physical and cultural. Based upon our analysis, we argue that ayahuasca purging should not be dismissed as a drug side effect or irrational belief but reconsidered for its potential therapeutic effects.