This study of 124 community adults examined whether perfectionism interacts with mindfulness and self-compassion to predict anxiety and depressive symptoms over two years. Participants completed measures of self-critical (SC) and personal standards (PS) higher-order dimensions of perfectionism at Time 1; mindfulness and self-compassion domains and facets at Time 2 one year later; and general distress (i.e., shared between depression and anxiety), anxious arousal, and anhedonic depressive symptoms at Time 1, Time 2, and Time 3 two years after baseline. In contrast to PS, SC perfectionism was associated with lower mindfulness and self-compassion domains and facets. Hierarchical regression analyses of moderator effects demonstrated that individuals with higher Time 1 SC perfectionism and lower Time 2 domain mindfulness or self-compassion had higher Time 3 general distress symptoms than others, adjusting for the effects of Time 1 and Time 2 symptoms. SC perfectionism also interacted with specific facets of mindfulness (i.e., observing, nonreactivity) and self-compassion (i.e., self-kindness, mindfulness, over-identification) to predict Time 3 general distress and/or anxious arousal symptoms. These findings highlight the importance of fostering mindfulness and self-compassion to reduce vulnerability to anxious and depressive symptoms in individuals with higher SC perfectionism.