This article aims to explore the experiences of science instructors who are active participants in the design and enactment of an interdisciplinary science course with student-centered pedagogy in a large-enrollment class. The data were collected through interviews with instructors and analyzed using the inductive thematic approach. Results show that the instructors discussed the benefits and challenges of using the previous passive-lecture format of the science course. Instructors believed that even though the previous format is easy to implement, it does not help students understand how scientists approach complex problems. In the new approach, the instructors prepared learning objectives to address expected learning outcomes. They integrated diverse research-based instructional strategies to enhance students' learning and interest in science but encountered some challenges. The instructors' experiences illustrate that planning and enacting an interactive science learning with an interdisciplinary approach is possible in undergraduate science education with appropriate support. The findings of this study can be a model for other universities to initiate changes in science instruction.