BackgroundBullying perpetration is a well-established risk factor for depression. One potential explanation for the elevated depression levels among perpetrators is reduced self-compassion resulting from the process of dehumanisation during bullying perpetration, while the effects of this may vary across cultures. ObjectiveTo explore the potential role of two dimensions of self-compassion, namely compassionate and uncompassionate self-responding, in the relationship between bullying perpetration and depression, considering cultural differences. Participants and setting3,982 adolescents aged 12–18 years from Hong Kong, Taiwan, United Kingdom, and the Netherlands completed questionnaires regarding traditional bullying and cyberbullying perpetration, self-compassion, and depressive symptoms. MethodsModerated mediation analyses were conducted, considering a potential moderating effect of Eastern and Western culture. Subgroup analyses were conducted to explore cross-cultural differences in the mediation models. ResultsSignificant associations were found between cyberbullying perpetration and depressive symptoms (β = 0.06, SE = 0.02, p = 0.007). Uncompassionate self-response partially mediated the association between traditional bullying perpetration and depressive symptoms (β = 0.08, SE = 0.01, p < 0.001). A significant interaction effect was found between traditional bullying perpetration and culture in predicting compassionate self-responding (β = 0.11, SE = 0.04, p = 0.002). The association between traditional bullying perpetration and compassionate self-responding was identified only in Western participants (β = 0.12, SE = 0.02, p < 0.001). ConclusionsUncompassionate self-responding mediated the association between traditional bullying perpetration and depression. Interventions and prevention programs should target uncompassionate self-responding among bullying perpetrators to prevent depressive symptoms. The distinct and culturally-specific roles of compassionate and uncompassionate self-compassion were supported, providing insights into the internal structure of self-compassion and its role in bullying behaviour.