Biology education emphasises producing scientifically literate students, mastering biological knowledge, and developing critical thinking. However, in reality, biology instruction only focuses on academic achievement in the Indonesian biology curriculum. Previous research has found that scientific inquiry is a practical approach to improve academic achievement and scientific literacy. Interactive socio-scientific inquiry (ISSI) was developed based on a distinctive inquiry approach. The ISSI uses socio-scientific issues as a learning context and uses digital technology as an interaction platform. This research used a quasi-experimental design with a pre-test-post-test non-randomised control group involving 196 tenth-grade students. The findings revealed substantial differences in learning outcomes between ISSI students with conventional and classroom discussion teaching methods. The ISSI students have significant enhancements in scientific literacy, biological knowledge, and critical thinking. These findings suggest the utility of using socio-scientific issues (to be criticised and resolved) and digital technology (with its interactive involvement as a learning interaction platform) to complement inquiry in biology teaching. The ISSI is an alternative method to support biology teaching in becoming more creative and encourages secondary school students to be more critical in learning content.