Abstract Objectives Recent studies suggest that children’s emotional difficulties may impact their parents’ psychological well-being, and certain protective factors could mitigate this association. The existing literature points to self-compassion as a potential protective factor against stress and difficulties. To this end, the present study aimed to explore the potential protective role of parents’ self-compassion in the prospective relationship between children’s emotional regulation difficulties and parents’ depressive symptoms. Method The initial sample consisted of 214 children (53.3% girls; Mage = 12.71, SD = 1.37) and their parents: 209 mothers (Mage = 46.74 years, SD = 4.42) and 181 fathers (Mage = 48.85 years, SD = 5.42). The participants answered self-report questionnaires in a two-wave longitudinal study conducted over one year. A multilevel analysis was performed to examine the predictive pathways of parents’ depressive symptoms from children’s emotional regulation difficulties, parents’ self-compassion, and their interaction. Gender differences were addressed in the predictive associations. Results Children’s emotional regulation difficulties predicted their parents’ depressive symptoms after one year, and this association was found to become attenuated as parents’ self-compassion increased. No significant gender differences were found for depressive symptoms or self-compassion, and parents’ gender did not moderate any of the longitudinal associations. Conclusion Children’s emotional regulation difficulties may increase risk for parental depressive symptoms, but parental self-compassion mitigates this relationship. Preregistration This study was not preregistered.