Objective: This study examines the dual mediating effects of acculturative stress and self-es teem on the relationship between social support and depression in multicultural adolescents. Methods: The structural relationships of latent variables were examined using SPSS and AMOS, based on data from 1,177 multicultural adolescents who participated in the Fourth-Year(2014) Multicultural Panel Survey. Results: Control variables such as gender, academic performance, and subjective health were identified as factors influencing depression. Family support and peer support not only demonstrated direct effects on depression but also showed indirect effects through partial mediation by acculturative stress and self-esteem. Meanwhile, teacher support exhibited a fully mediated effect on depression only through self-esteem. Conclusions: Based on the results, this study suggests practical interventions to prevent depression by enhancing social support and self-esteem while reducing acculturative stress among multicultural adolescents.