Background: In the context of increasing scientific interest in the potential therapeutic use of psychedelic agents and their underlying psychotherapeutic mechanisms, we undertake the first detailed assessment of insights and life and lifestyle changes associated with ayahuasca consumption. Methods: An international cross-sectional study of ayahuasca drinkers in a variety of settings was performed (n = 8907). Bivariate analysis and multivariate linear and logistic regressions were used to explore associations between a range of covariates and insights, life changes and lifestyle changes. The least absolute shrinkage and selection operator variable selection method (LASSO) was used to select the variables most relevant for inclusion in models assessing broader wellbeing and mental health associations. Results: Insights are almost universally reported as part of the ayahuasca experience and are highly valued by drinkers and strongly predictive of subsequent beneficial life and lifestyle changes. A range of personal, vocational, religious/spiritual and health-related life changes (attributed to ayahuasca) are also commonly identified, as are various beneficial lifestyle and health behavior changes. Demographic and ayahuasca drinking variables that are predictive of such phenomena are reported, along with associations between insights, life and lifestyle changes and perceived growth in psychological wellbeing and current mental health status (Kessler 10 and SF-12 MCS). Conclusion: Insights and subsequent life and lifestyle changes appear to have a central role in the transformative effects reported by individuals consuming ayahuasca, with these occurring across contexts of use and demographic groups.