The senior high school period is a critical phase for the proliferation of mental health problems, as well as a key period for cognitive development among adolescents. Due to the importance of support from the external environment for students, this study aims to explore and verify the protective role of social support in the mental health and creative tendencies of senior high school students, as well as its mechanisms and boundary conditions. Based on a survey of 1463 Chinese senior high school students, a moderated mediation model was constructed. The results showed that (1) perceived social support significantly negatively predicts mental health problems and significantly positively predicts creative tendencies; (2) self-esteem mediates the impact of perceived social support on both mental health problems and creative tendencies; (3) perceived stress not only moderates the impact of self-esteem on mental health problems and creative tendencies, but also moderates the mediating effect of self-esteem. The findings of this study shed light on the positive impact of social support and the self-esteem it nurtures during the senior high school years. These insights offer valuable recommendations for practitioners aiming to prevent mental health issues and foster creative tendencies among senior high school students.