Objective: Ayahuasca is a hallucinogenic plant preparation, traditionally consumed in sacred ceremonies by indigenous North‐Westerner Amazonian countries like Colombia, Peru, Brazil, and Ecuador. It is fundamental to carefully balance bene!ts/risks related to the ayahuasca intake, both during ceremonies and experimental settings. The aim is at evaluating and comparing the potential therapeutic bene!ts versus health risks related to ayahuasca intake (both acutely and chronically), focusing on its application in psychedelic psychiatry. Design: A comprehensive mini overview focusing on psychiatric outcomes following ayahuasca intake both in healthy volunteers and in clinical samples. Results: Preclinical, observational, and experimental studies in healthy volunteers as well as in clinical samples suggest that ayahuasca may be bene!cial as an antidepressant, emotional regulator, anxiolytic, and antiaddictive drug, by exerting fast‐acting and enduring clinical effects. Ayahuasca appears to be safe and well tolerated, nausea and emesis being the most reported and transient side e"ects. Some findings suggest not to use ayahuasca in bipolar or psychotic patients because of an increased risk of manic switch and/or psychotic onset. Conclusions: Further research should be carried out in randomized, double‐blind, placebo‐controlled trials, by implementing neuroimaging studies, in order to better evaluate therapeutic potential of ayahuasca in mental disorders.