Objective <p>To investigate the relationship between third-trimester antenatal depression (AND) and the number of pregnancies, considering the possible moderating role of dysmenorrhea.</p> Methods <p>A total of 1,178 pregnant women in their third trimester were included in this cross-sectional observational study. The pregnant women were categorized into those with and without dysmenorrhea. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS), a validated instrument for perinatal depression screening applicable to both antenatal and postnatal populations. Regression analysis and simple slope analysis to evaluate the moderating effect of dysmenorrhea.</p> Results <p>The non-dysmenorrhea group exhibited significantly higher age, pre-pregnancy BMI, number of pregnancies or deliveries, and lower EPDS scores than the dysmenorrhea group (<i>p</i> &lt; 0.05). In both groups, an inverse relationship was observed between educational levels and EPDS scores (<i>p</i> &lt; 0.001). For the non-dysmenorrhea group, age was inversely related to the EPDS scores (<i>p</i> &lt; 0.001). Within the dysmenorrhea group, the number of Pregnancies and the count of deliveries demonstrated a positive association with EPDS scores (<i>p</i> &lt; 0.001). A negative correlation with EPDS scores was found for both age and the educational levels of the husbands (<i>p</i> &lt; 0.05). Dysmenorrhea was linked to a positive correlation with EPDS scores (<i>p</i> &lt; 0.001). Furthermore, the interaction between the number of pregnancies and the presence of dysmenorrhea also demonstrated a positive correlation with EPDS scores (<i>p</i> &lt; 0.05).</p> Conclusion <p>In conclusion, there is a significant positive link between the number of pregnancies and AND, with further exacerbation by dysmenorrhea.</p>