BACKGROUND: Epidemiological studies indicate that 12% to 50% of university students suffer from one or more common mental health problems, which may be linked to academic performance. However, most current studies provide associations between only a single mental disorder and college students' academic performance, with inconsistent results, and do not consider gender differences. The objective of this study was to analyze the mental health status across various dimensions among male and female college students and to explore the impact of gender on the relationship between mental health status and academic performance. METHODS: This study used a cross-sectional design conducted at an undergraduate medical school in Shanghai, China. Data were collected from undergraduate students in the 2020-2021 academic year, with a total of 6923 students (2153 males and 4770 females) completing the survey. The SCL-90 scale was used to screen for mental health problems. Data on student academic performance were obtained from school records. Logistic regression were used to examine the association between mental health status and academic performance. RESULTS: The overall positive rate for the mental health status of the participants was 41.2%, with 39.6% for males and 41.9% for females. Among female students, those with positive mental health were more likely to underperform academically (aOR = 1.183, 95% CI: 1.035-1.353, p <
0.05). As the severity of symptoms in the factors of somatization (SOM), interpersonal sensitivity (INTS), depression (DEPR), paranoid ideation (PARI), psychoticism (PSY), and sleep and diet (ADD) increases, the likelihood of poor academic performance also increases in females. However, mental health status among male students is not related to academic performance (aOR = 1.138, 95% CI: 0.950-1.364, p >
0.05). CONCLUSIONS: The poor mental health status of female college students was significantly correlated with a higher likelihood of poor academic performance, and there was a dose-dependent relationship between the six factors of the SCL-90 and academic performance. In contrast, no similar results were observed among male students.