Background: During the epidemic, the mental health of college students was generally poor, especially anxiety and depression, which should be treated using counseling and intervention. This study aimed to observe the influence of dialectical behavior therapy on the anxiety and depression of medical students during the normalization of the prevention and control of the COVID-19 epidemic.Methods: A total of 26 medical students (experimental group) were treated with dialectical behavior therapy intervention for 4 weeks. Changes in depression, anxiety, and stress levels were assessed by the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder (GAD-7) scale, the Somatic Self-rating Scale (SSS), and the Perceived Stress Scale (PSS-10). This group was compared with 26 medical students (control group) without intervention.Results: The value-added scores of the PHQ-9 (t=2.543, P=0.014) and GAD-7 scales (t=3.790, P=0.000) in the experimental group were significantly higher than those in the control group, while in the SSS scale, the value-added score of the depressive symptoms subscale (t=2.234, P=0.030) in the experimental group was significantly higher than that of the control group. For the total score of the PSS-10 scale (t=2.435, P=0.018), the value-added score of the experimental group was significantly higher than that of the control group. Conclusions:The intervention of dialectical behavior therapy can effectively alleviate the depression and anxiety of medical students during the normalization of epidemic prevention and control.