This study explores the perceptions of culturally relevant science teaching of 35 teachers of American Indian students. These teachers participated in professional development designed to help them better understand climate change science content and teaching climate change using both Western science and traditional and cultural knowledge. Teacher perceptions of practices using culturally relevant instruction were evaluated. The data were analyzed both quantitatively and qualitatively. The results from the survey analysis show that the teachers' existing practices of culturally relevant science teaching were limited in choosing topics relevant to American Indian culture. We found three common themes from the teachers' perceptions of culturally relevant science teaching, meaning of culturally relevant science teaching, teaching strategies, and purpose of culturally relevant science teaching from the qualitative data. We also found that teachers with higher survey scores perceive culturally relevant science teaching differently than teachers with lower survey scores, specifically for the purposes and teaching strategies of culturally relevant science teaching. The results show that teachers with higher survey scores tended to perceive culturally relevant science teaching as a two-way learning process between teachers and students where the teachers can learn traditional science knowledge from the students. They also tend to perceive using concrete traditional science examples as effective teaching strategy for culturally relevant science teaching and building strong relationships with American Indian students as the most important purpose of culturally relevant science teaching. We also discuss common challenges faced by science teachers when trying to implement culturally relevant science teaching with American Indian students.