Although there are effective alcohol and drug prevention programs available for Australian secondary schools, no effective culturally-inclusive programs exist for Aboriginal and/or Torres Strait Islander students. To address this gap, we developed the Strong & Deadly Futures program for young people aged 12–14 years. The web-based program was developed with Aboriginal, Torres Strait Islander and non-Indigenous staff and students at four secondary schools (2 urban, 2 rural). This mixed-methods study reports on qualitative and quantitative feedback from students (n = 235) and school staff (n = 8) in a pilot trial to assess acceptability and feasibility of this curriculum-aligned program. Feedback indicated that students were highly engaged and motivated to learn as a result of the story-based mode of delivery, and teachers reported the ease of program implementation and adaptation. Implications for future school-based health program development are discussed. Overall, Strong & Deadly Futures appears to be an acceptable and feasible culturally-inclusive alcohol and drug prevention program. Further research will test the program's efficacy in a randomised controlled trial.