Background and Aim: Mental health is a fundamental component of overall health, and spiritual and religious factors may play an important role in its promotion. Despite growing evidence on the role of religiosity in mental health, research examining the associations of Quran engagement and religious orientation with mental health among university students remains limited and, in some cases, inconsistent. This study aimed to investigate the associations of Quran engagement and religious orientation with mental health among students at Kurdistan University of Medical Sciences. Materials and Methods: This descriptive-analytical cross-sectional study was conducted among 237 students at Kurdistan University of Medical Sciences. Participants were selected using a two-stage cluster sampling method. Data were collected using the 28-item General Health Questionnaire (GHQ-28), the Quran Engagement Questionnaire, and Allport’s Religious Orientation Scale. Spearman’s rank correlation coefficient was used to examine associations between variables, and multiple linear regression analysis was performed to identify factors associated with mental health. Statistical significance was set at p < 0.05. Results: The mean scores for mental health problems, Quran engagement, and religious orientation were 28.57 ± 13.04, 61.12 ± 14.68, and 64.78 ± 10.68, respectively. Quran engagement was weakly but significantly negatively correlated with overall mental health problems (rₛ = −0.147, p = 0.024), as well as with social dysfunction (rₛ = −0.198, p =0.002) and depression (rₛ = −0.156, p=0.016). Intrinsic religious orientation was also negatively and significantly correlated with overall mental health problems (rₛ = −0.128, p=0.049) and depression (rₛ = −0.198, p>0.002). In contrast, extrinsic religious orientation was not significantly correlated with overall mental health problems (rₛ = 0.008, p<0.906) or any of its subscales. In the multiple regression model, after adjustment for demographic variables, only the faculty in which students were enrolled was significantly associated with mental health problems. Neither Quran engagement nor religious orientation remained significantly associated with mental health problems in the adjusted model. Conclusion:Greater Quran engagement was associated with fewer mental health problems, particularly lower levels of depression and social dysfunction, and was more closely related to intrinsic rather than extrinsic religious orientation. However, neither Quran engagement nor religious orientation was an independent predictor of mental health problems after adjustment for demographic characteristics. Longitudinal studies are warranted to clarify the temporal and potentially causal relationships between Quran engagement, religious orientation, and mental health and to identify other determinants of students’ mental health.