We investigate the mental health of multicultural families (CFs) in South Korea, identify risk factors, and propose interventions to improve mental health. Adults over 19 years of age were analyzed using the Community Health Survey 2019 in South Korea, consisting of 228,952 individuals including 3,524 from multi-CFs. We employed chi-squared tests and multiple logistic regression to compare mental health between multi- and mono-CFs, exploring the influence of various factors. Multi-CFs had significantly higher levels of stress recognition (P-value = 0.010) and experiences of extreme sadness or despair (P-value = 0.002) than mono-CFs. In multi-CFs, younger group, households with lower income and people with unhealthy behaviors regarding walking or sleeping were at risk of mental health. Socially isolated families, relative to the families participating in active social gatherings, had about a 1.36 times higher risk of stress, 2 times higher experiences of extreme sadness or despair and 5.32 times higher depressive symptoms. Multi-CFs are vulnerable to mental health problems, and even within multi-CFs, groups with relatively low socioeconomic status should be prioritized since problems are more significant among them. Activated social networks can help multi-CFs integrate into society and promote mental health.