The Mental health of Palestinians has been described as among the lowest in the world, with over half of Palestinian adults meeting the diagnostic threshold for depressive symptoms and a significant portion of Palestinians experiencing mental distress and anxiety. The aim of the current study was to test the correlation between quality of life (QoL) and mental health outcomes, and the role of sociodemographic variables in predicting mental health outcomes (depression, anxiety, and stress) among Palestinian adults during a challenging period of political conflict. The sample of our study consisted of 957 participants, 283 males and 674 females they were recruited using online methods; online advertisements, e-mail campaigns and social media. Our findings showed that QoL negatively correlated with stress (r = − 0.43, p < 0.01), anxiety (r = − 0.46, p < 0.01), and depression (r = − 0.47, p < 0.05). Moreover, stress positively correlated with anxiety (r = 0.81, p < 0.01), and depression (r = 0.89, p < 0.01). Finally, anxiety positively correlated with depression (r = 0.82, p < 0.01). Results of hierarchical regression analysis to predict stress, anxiety and depression, indicated that QoL, educational level, gender, region of residence, and age explained in a significant way variance in depression, anxiety and stress. Our findings are promising to conduct other studies in order to understand better how current study variables correlate to each other, so appropriate clinical interventions to mitigate the negative effects of depression, anxiety, and stress through enhancing quality of life and positive coping strategies can be developed and implemented by mental health providers.