College students are often experience increased stress and anxiety, that increases the risk of depressive symptoms. Aim: Investigate the role of psychological flexibility, mindfulness traits, and perceived social support as predictors of psychological symptoms. Methods: The current study employed a descriptive cross-sectional approach. The study was done in nursing faculty, Mansoura University. The number of participants in this study was 551.Four tools were used: Depression Anxiety Stress Scales-21, Acceptance and Action Questionnaire-II (AAQ-II), the Multidimensional Scale of Perceived Social Support (MSPSS), and Mindfulness Attention Awareness Scale (MAAS). Results: indicates that (18.7%) of nursing students experience mild to severe depressive symptoms. Whereas, (69.9%) of them had high psychological flexibility, (30.1%) had low psychological flexibility and there is a positive significant correlation between psychological flexibility and depressive symptoms. On the other hand, there is a negative correlation between mindfulness and perceived social support and depressive symptoms. Conclusion: This study concluded that, psychological flexibility, mindfulness traits, and perceived social support act as predictors of depressive symptoms. Recommendations: This work may have important implications for clinical training and practice, college students may benefit from mindfulness-based interventions for enhancing psychological flexibility, consequently decreasing the risk for depressive disorders.