Interest in research into the treatment of mental disorders with the help of psychedelics as tools in psychotherapy is once again on the rise. One of the psychedelics is ayahuasca, a DMT-containing brew made from two plants and used by the people of the Amazon for thousands of years in a ritual context for spiritual and health purposes. Due to the growing popularity of this psychedelic around the world, we conducted a qualitative study of retrospective reports of meaningful ritual experiences with ayahuasca. The aim of the study was to better understand the helpful aspects of the self-perceived therapeutic experience with ayahuasca and the self-perceived changes in symptoms of depression and mental well-being. Among the candidates that we obtained through public calls in various ayahuasca groups on the social network, we included seven individuals (five women and two men), of whom four were Americans, two Canadians, and one Colombian. Participants ranged in age from 21 to 57, were highly educated, and were fluent in English. They completed the Depression Questionnaire and participated in semi-structured interviews conducted through a video call. We analyzed the interviews within the methodological framework of grounded theory. The qualitative results have shown that a helpful aspect for a self-perceived transformative experience with ayahuasca is preparedness for change before the ceremony. During the ceremony, a helpful aspect was the altered state of consciousness marked by visions and voices representing real world as well as imaginary content. The altered state of consciousness promoted psychological processes of change, such as experiencing bodily sensations, deepened emotions, insights, corrective experiences, and trauma memory reliving and processing. Because experiences were often difficult, participants’ recognition of support was also regarded as a helpful aspect. Particularly important for change were the mystical experiences of individuals marked by spiritual insights. In general, all participants perceived an improvement in depression symptoms and positive changes in areas of mental well-being that were the strongest felt in the weeks after the ceremony. Some participants reported an intense and rapid improvement in mental state after the ritual. We hypothesize that the self-perceived therapeutic effects of ayahuasca depended on the psychological processes of change that were triggered by the synergistic action of the substance’s pharmacology and the context in which it was ingested. For our sample, ayahuasca was a catalyst for therapeutic processes.