Computer-based classroom simulations have been argued to be a promising way to practice preservice teachers’ (PSTs’) interpersonal competence and to ease the gap between teacher education and educational practice. The systematic literature review presented in this paper examined existing research on the links between PSTs’ interpersonal competence, well-being, and simulations. Furthermore, this review mapped learning experiences, affordances, and hindrances of simulations. Fifteen studies were found eligible for inclusion. Most of these studies reported positive effects of simulations on PSTs’ classroom management and teaching skills in general, rather than specifically on interpersonal competence (e.g., professional interpersonal vision, professional interpersonal knowledge, professional interpersonal repertoire). Concerning PSTs’ well-being, four studies did show positive effects of simulations on PSTs’ self-efficacy. However, none of the studies reported PSTs’ anxiety. Reported affordances were mostly educational (e.g., receiving teacher feedback, available resources) or social (e.g., peer observation, discussions), while the reported hindrances were mainly of a technical nature (e.g., lack of a user-friendly interface, malfunctioning audio or video). Positive learning experiences depended on the degree of realism and authenticity within the simulation. The results of this study provide suggestions for future research on how computer-based simulations in teacher education could contribute to PSTs’ interpersonal competence and well-being.