Increasing cross-border mobility and migration in today’s globalized world gives rise to culturally diverse schools, which calls for new practices of school leadership and classroom instruction. Focusing on the notion of culturally responsive instructional leadership, this study aims to empirically examine whether effective principal leadership may alleviate teachers’ perceived challenges associated with teaching immigrant-background children. The data came from the Korea Multicultural Education Survey 2017. A portion of the data was used in this study, i.e., the portion collected from teachers whose schools were located in areas of immigrant residential concentration. The results clearly showed that the proportion of immigrant-background children at school was positively associated with the level of teachers’ perceived challenges. However, such an association became weaker as principal leadership was performed to a greater degree in a culturally responsive way. It appears that the increase in teachers’ instructional uncertainty arising from student diversity does not necessarily result in the increase in their perceived challenges. The principal’s culturally responsive leadership may moderate the relationship between student diversity and teachers’ perception of it as a source of difficult challenges.