Co-existence of depression and anxiety can be associated with severe detrimental consequences to the physical, mental and social wellbeing of the affected populations. This study was conducted to determine prevalence of depressive and anxiety symptoms among Palestinian medical students and to investigate associations between sociodemographic factors of the students with depressive and anxiety symptoms. This study was conducted in a cross-sectional observational design using a questionnaire in the period between September 2018 and April 2019 in a major university in the West Bank of Palestine. Depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II) and anxiety symptoms were assessed using the Beck Anxiety Inventory (BAI). The questionnaire also collected the sociodemographic characteristics of the students. Reliability of the questionnaire was tested using the test re-test method. A total of 425 medical students were invited to participate in the study. Of those invited, 286 students completed the questionnaire, giving a response rate of 67.3%. More than half (56.6%) of the students had minimal depression, 20.3% had mild depression, 14.0% had moderate depression, 9.1% had severe depression, 23.4% had no anxiety, 29.7% had mild to moderate anxiety, 25.5% had moderate to severe anxiety, and 21.3% had severe anxiety. Multiple linear regression analysis showed that academic stage (p-value < 0.01), Grade Point Average (p-value < 0.01), mental health status (p-value < 0.001), ever attempted suicide (p-value < 0.05), and religious commitment (p-value < 0.01) were predictors of BDI-II scores. Multiple linear regression analysis showed that academic stage (p-value < 0.05) and mental health status (p-value < 0.001) were predictors of BAI scores. Depressive and anxiety symptoms were prevalent among Palestinian medical students in a major university in the West Bank of Palestine. Interventions might be designed to improve self-rated mental health of medical students in their academic years, ameliorate study conditions, and provision of counseling services to improve spirituality might be effective in reducing symptoms of depression and anxiety among medical students in Palestine. Future studies are still needed to investigate if these interventions could be useful in reducing depressive and anxiety symptoms among Palestinian medical students.