The mental health of university students is a public health concern, as psychopathology has significantly risen among this population. Mindfulness-based programs may support their mental health, though more research is needed. We used a two-armed pilot randomized controlled trial to study the feasibility, preliminary effectiveness, and potential mechanisms of a brief 6-week instructor-led mindfulness- and compassion-based program (MCBP for University Life) on perceived stress and psychological distress. Thirty undergraduate psychology students participated (15 in the intervention group, and 15 as wait-list controls). Those in the intervention arm engaged well with the course and formal at-home practice, attending at least five sessions and meditating between 4-6 days per week. Significant improvements in perceived stress, psychological distress, mindfulness skills, decentering, self-compassion, and experiential avoidance were found at the end of the intervention, while the wait-list group remained unchanged. There were significant differences between the two groups in those variables at post-test, favoring the intervention arm with major effects. Reductions in stress were mediated by improvements in mindfulness skills, decentering, and self-compassion; meanwhile reductions in psychological distress were mediated by improvements in decentering. These results suggest that this intervention might be feasible and effective for university students, but more high-quality research is needed.