Chemical kinetics is widely recognized as one of the most challenging topics in secondary school chemistry due to its abstract nature and the difficulty students experience in connecting observable phenomena with underlying particle interactions. This study investigated the effectiveness of integrating interactive simulations with process-oriented Guided Inquiry Learning (POGIL) laboratory activities to enhance Grade 11 students’ conceptual understanding, achievement, confidence, and engagement in chemical kinetics. The study employed a Design-based research (DBR) approach within a mixed-methods framework and was conducted with 63 Grade 11 students at Tana Haik Secondary School in Bahir Dar, Ethiopia. Quantitative data were collected through pre- and post-tests, confidence measures, and engagement questionnaires, while qualitative data were gathered through student interviews, teacher interviews, classroom observations, and group discussions. Quantitative data were analyzed using descriptive statistics, paired-samples t-tests, effect size measures, and percentage distributions, whereas qualitative data were analyzed thematically. The findings revealed significant improvements across all learning outcomes. Students' achievement increased from a mean score of 9.65 to 21.19 out of 32 (d = 4.03), confidence from 6.38 to 13.08 out of 16 (d = 1.94), and engagement from 3.10 to 4.45 on a five-point scale (d = 2.30). Conceptual understanding also improved substantially. Qualitative findings showed that collaborative inquiry, simulation-based exploration, and guided learning enhanced students' participation, motivation, scientific reasoning, and ability to connect macroscopic, microscopic, and symbolic representations. However, some learners still required teacher support to interpret complex microscopic processes. The study concludes that integrating interactive simulations with POGIL laboratory activities creates a more engaging, student-centered, and conceptually meaningful learning environment for secondary school chemistry.