Understanding the factors that influence psychological distress in youth is critical for effective mental health intervention. This investigation aims to elucidate the interrelations among mental health self-stigma, mindfulness, and psychological distress among youth in Johor, Malaysia. Self-administered questionnaires were employed, incorporating validated scales such as the Internalized Stigma for Mental Illness Scale-10 (ISMI-10), Five Facet Mindfulness Questionnaire (FFMQ-15), and the General Health Questionnaire (GHQ-12). Statistical analyses included descriptive statistics, Pearson correlation, and multiple regression. The result shows that the majority of respondents exhibited moderate levels across the evaluated variables: mental illness self-stigma, psychological distress self-stigma, mindfulness, and psychological distress. Pearson correlation analyses revealed that self-stigma associated with mental illness and psychological distress were positively correlated with psychological distress. In contrast, mindfulness exhibited a negative correlation to psychological distress. Multiple regression analyses identified both psychological distress self-stigma and mindfulness as significant predictors of psychological distress levels among the youth in Johor. Meanwhile, mindfulness emerged as the most potent unique predictor. This study underscores the importance of both psychological distress self-stigma and mindfulness in influencing psychological distress levels among youth. These findings may serve as a pivotal foundation for future interventions aimed at mitigating psychological distress among youth. The study's results have significant implications for mental health policies and programs, emphasizing the need to address both self-stigma and mindfulness to effectively manage psychological distress in youth.