ABSTRACT Psychedelics can facilitate mystical-type insights and beliefs, such as the belief that the fundamental nature of reality is loving consciousness. These belief changes could underlie the positive effects of psychedelics on wellbeing. However, mystical-type beliefs have been criticized of being delusional, as they contradict naturalism. Here I argue that naturalism is one metaphysical position among several competing ones. There is no definite way of choosing one metaphysical theory over others, as there are several metaphysical positions that are internally consistent and compatible with scientific knowledge. This calls for metaphysical agnosticism, which entails that psychedelic-facilitated metaphysical beliefs cannot be considered as delusional simply if they contradict naturalism. However, the challenge is to distinguish between beliefs that are strictly metaphysical and other mystical-type beliefs, which can include, for example, paranormal beliefs. Metaphysical agnosticism does not apply to the latter and they can be considered as problematic. I apply metaphysical agnosticism to evaluate mystical-type belief changes associated with the use of psychedelics, as indicated by empirical research. I consider the possibility that mystical-type beliefs are ineffable and non-conceptual, which entails that we should not take conceptualizations of them too seriously. I conclude by discussing the implications of metaphysical agnosticism for psychedelic-assisted therapy.