Prejudice toward marginalized groups is recognized as a complex and harmful social issue. The present study investigates the role of polyculturalism in undermining prejudice toward lesbian, gay, bisexual, transgender, and intersex people and refugees. A pilot study (N = 76) compared participants' prejudice, contact, and moral exclusion toward lesbian, gay, or bisexual (LGB) and transgender or intersex (TI) people. There were differences for three out of four variables; thus, LGB and TI variables were separated in the study proper (N = 154). In this study, we investigated moral exclusion and contact (quantity and quality) relating to LGB, TI, and refugee groups as simultaneous mediators of the relationship between polyculturalism and prejudice, while taking into account openness as per previous research. Structural equation modeling indicated that moral exclusion and contact quality acted as mediators between polyculturalism and prejudice for LGB people, TI people, and refugees.