Background and Objective Insomnia is very common in depression and especially medical students are easy to experience sleep disturbance because of their studies. Also depressive symptoms are closely related to stress. Stress is an interaction between an individual and the environment, involving subjective perception and assessment of stressors, thus constituting a highly personalized process. Different personality traits can create different levels of stress. In this study, we tried to explore the relationship between insomnia and depressive symptoms or stress of medical students, and whether their personality may play a role on this relationship or not. Methods We enrolled 154 medical students from University of Ulsan College of Medicine. We used the Medical Stress Scale, the Multidimensional Perfectionism Scale, the Patient Health Questionnaire-9, the Academic Motivation Scale, the Insomnia Severity Index, and The revised NEO Personality Inventory (PI). Results Insomnia severity, amotivation, medical stress, mental health index and neuroticism traits of NEO-PI significantly correlated with depressive symptom severity (p < 0.001). And stepwise linear regression analysis indicated insomnia, amotivation and neuroticism traits of NEO-PI are expecting factors for students’ depressive symptoms is related to (p < 0.001). Conclusions Student who tend to be perfect feel more academic stress. The high level of depressive symptom is associated with insomnia, amotivation, academic stress in medical student. Moreover, personality trait also can influence their depressive symptoms.