The paper describes an analysis of the questions posed by high school students regarding relationships between science and religion in a series of debates with scientists in public high schools of the northern part of Portugal. The exploratory interpretation of 171 collected anonymous written questions allowed for the detection of fragilities in the students’ ideas about the nature of science and the nature of religion, connected with a trend to reject religion using scientism arguments. The findings reinforce a need of revising the fragmented teaching of nature of science and its connections with religion towards a more contextualized approach of diversified episodes of these social endeavours, anchored in life’s ‘big questions’ that allow students to make cross-disciplinary connections. Our analysis also supports the need for more research on students’ questions rather than on students’ answers in more common research methodologies conducted to inform the development of a more meaningful curriculum.