Experiential avoidance, considered a main process of psychological inflexibility, has been defined as the unwillingness to be in contact with particular unwanted inner experiences and the effort to control or avoid its form, frequency and the context in which they occur. On the other hand, decentering, conceptualized as the ability to deal with feelings, thoughts and emotions as subjective and ephemeral events, which occur in the mind, is considered an important protective process against psychopathology. The present study aimed to explore the moderator effect of two different emotional regulation processes, decentering and experiential avoidance, on the association between external shame and depression. The sample comprised 421 participants (131 males and 290 females), aged between 18 and 34-year-old. Results from two independent path analysis revealed that decentering abilities and experiential avoidance showed a significant moderator effect on the association between external shame and symptoms of depression. In fact, these findings allow to verify that decentering abilities were negatively linked to symptoms of depression. Through a path analysis, the buffer effect of decentering was confirmed. On the contrary, performed tests demonstrated that experiential avoidance exacerbates shame's impact on the severity of depressive symptoms. Taken together, these findings emphasize the importance of targeting maladaptive emotion regulation processes (such as experiential avoidance), and developing adaptive strategies (e.g., decentering abilities), as strategies to diminish depressive symptomatology in prevention and intervention programs.