Emotional flexibility can be defined as the ability to respond in a context-appropriate emotional manner and recover from one’s initial emotional responses when the context changes. Emotional flexibility has been associated with psychological health. Mindfulness and self-compassion have both been associated with various aspects of well-being and are considered buffers against psychopathology; however, few studies have examined the relationships of mindfulness and self-compassion with emotional flexibility. A total of 417 participants were recruited through an online crowdsourcing website and completed study questionnaires as well as negative and positive mood induction procedures. Results indicated that both mindfulness and self-compassion were significantly and positively associated with mood drops and mood increases in response to negative and positive mood induction procedures, respectively. We also found that depressive symptoms and depression-related negative cognitions were negatively correlated with emotional flexibility. Further, hierarchical regression analyses revealed that self-compassion may explain variance in emotional flexibility beyond what is accounted for by trait mindfulness. Findings of this study underscore the importance of mindfulness and, specifically, self-compassion as likely key factors in emotional flexibility. Further, it appears that self-compassion may explain some aspects of emotional flexibility beyond variance contributed for by trait mindfulness alone, suggesting that both these constructs may need to be cultivated directly in psychological interventions for optimal psychological health. Future work should replicate and extend our findings and examine directionality among the examined factors.