This study compared mental health problems and psychiatric treatment experiences between mothers of twins and mothers of singletons, controlling for assisted reproductive technology (ART), perceived family support (PFS), and demographic covariates. Participants were 1592 South Korean mothers, including 853 mothers of singletons (M = 36.6 years, SD = 3.6) and 739 mothers of twins (M = 38.3 years, SD = 4.9), who completed an online survey assessing the General Health Questionnaire (GHQ), psychiatric treatment experience (PTE), PFS, ART use, and demographic factors. Hierarchical regression, analysis of covariance (ANCOVA), and logistic regression analyses were conducted with GHQ as the outcome variable. PTE was analyzed both as a dependent variable and as an independent variable. ART use significantly predicted GHQ scores beyond PFS, PTE, and demographics in both groups. After adjusting for all covariates, mothers of twins had higher GHQ scores than mothers of singletons, although the effect size was small (Cohen’s d = 0.16). Logistic regression revealed that mothers of twins were more than twice as likely to have received psychiatric treatment compared to mothers of singletons (odds ratio = 2.5, 95% CI [1.8, 3.4]). These results indicate that mothers of twins experience greater mental health challenges than mothers of singletons, indicating the importance of tailored mental health screening, prevention, and intervention programs for this vulnerable group.