Today, school bullying is considered an important social problem that causes developmental injuries and health issues in bullies and victims. The present study investigated the mediating role of brain-behavioural systems in relationships between school climate and emotional self-regulation with school bullying in high school students. This study had a cross-sectional correlational design. The sample size was 257, and the participants were selected using cluster sampling. They completed the Olweus Bully/Victim Questionnaire, Organizational Climate Index, Emotion Regulation Questionnaire, and Behavioural/Brain Systems Questionnaire. The data were analysed using the Pearson correlation coefficient and structural equation modelling (SEM). The findings revealed that the school bullying model based on the school climate and emotional self-regulation with the mediating role of brain-behavioural systems had a good fit. They also demonstrated that school climate had a direct negative effect on school bullying, whereas emotional self-regulation had a direct positive effect on it (p < 0.01). The school climate and emotional self-regulation were found to have a positive indirect effect on school bullying through the mediating role of brain-behavioural systems (p < 0.01). Therefore, it is necessary to develop plans to improve school climate, emotional self-regulation, and brain-behavioural systems to reduce school bullying.