Purpose: This study aimed to investigate the associations of the traits of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) with depression and empathy among medical students. Patients and Methods: A cross-sectional survey was conducted with 202 fifth-year students at a Japanese medical school for 10 months during their clinical clerkship. The survey included sociodemographic questions and validated tools to measure depressive symptoms (Hospital Anxiety and Depression Scale [HADS]), medical students' empathy for patients (Jefferson Scale of Empathy-Student version [JSE]), ADHD traits (ADHD Self-Report Scale Screener [ASRS Screener]), and ASD traits (Autism-Spectrum Quotient Japanese version-21 [AQ-J-21]). Results: A total of 151 students (response rate: 74.7%) participated in the survey. Of these, 41 (27.2%) reported a total score of ≥ 20 on the HADS and were categorized as depressed. Depressed students reported significantly lower and higher rates of having a part-time job and a history of enrolment in other faculties, respectively, than non-depressed students. According to the cutoff criteria of the ASRS Screener and AQ-J-21, 31 (20.5%) and 42 (27.8%) students reported ADHD and ASD traits, respectively. Multivariate regression analysis, controlling for age and sex, reported that higher age, ASRS Screener scores, and AQ-J-21 scores were significant predictors of higher HADS total scores. Additionally, higher AQ-J-21 scores significantly predicted lower JSE scores. Conclusion: The degree of ADHD and ASD traits was significantly associated with depression. Moreover, the degree of ASD traits was significantly associated with lower empathy for their patients. It is important to consider that about 20-30% of medical students have these neurodevelopmental traits and to develop intervention strategies for improving depression and empathy.