Polygyny is a common practice in a wide range of societies across the globe. Increasingly, many studies suggested that polygyny has a significant impact on mental health. This study aimed to investigate the impact of polygynous family structure on the mental health of students at Jazan University. A stratified sample of 489 undergraduate students, 379 of whom were from monogynous families and 110 were from polygynous families, participated in this study. The participants completed the Brief Symptom Inventory (BSI-18), the McMaster Family Assessment Device (FAD), and the Self-esteem Scale (SE). Independent-samples t-tests were employed to compare psychiatric symptoms, general family functioning, and self-esteem of students from polygynous families and students from monogynous families. Regression analysis was conducted to detect the main predictors of the study's dependent variables. The students from polygynous and monogynous family structures did not differ significantly in their scores on the scales of mental health, family functioning, and self-esteem. Low mother's education was significantly associated with the prevalence of polygynous family and was a strong predictor of poor family functioning. Female gender was significantly associated with more somatization (p<0.01) and anxiety (p<0.05) symptoms. The findings of the present study suggest that University students' mental health did not differ significantly with respect to their family structure. Implications for health practitioners, teachers, and policy makers are discussed. Future studies could investigate the impact of polygyny on mental health of children, adolescents, and fathers and mothers themselves.