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Purpose: The purpose of this study was to compare the factors related to depression between non-multicultural and multicultural middle school students. Methods: In this study, data were collected using structured questionnaires targeting students of 9 middle schools in G Province, Korea. Finally, the data of 304 students were analyzed by descriptive statistics, t-test, ANOVA, Pearson's correlation, and multiple regression analyses using SPSS 24.0. Results: The multicultural students showed a higher depression score (47.14±8.33) than the counterpart (44.22±8.11) (p<.001). The results of the multiple regression analysis revealed that academic stress (β=.33, p<.001), peer attachment (β=-.13, p<.02), and body image (β=.25, p<.001) were the influencing factors on depression in non-multicultural students. However, in multicultural students, depression was related to peer attachment (β=-.16, p=.03) and self-esteem (β=-.42, p<.001). Conclusion: To prevent and manage depression in non-multicultural middle school students, it is essential to help them relieve academic stress and build peer relationships and positive body image. For multicultural middle school students, helping them to have high self-esteem and peer attachment would be the first measure to prevent and manage depression.