This study aims to examine the influence of inquiry-based instruction on eighth-grade male and female students' motivation and engagement in science learning in two public junior high schools in central Taiwan. Mixed-methods methodology was adopted with 60 students (32 males and 28 females) in the experimental group and 56 students (28 males and 28 females) in the control group. The study lasted for one semester and six units using inquiry-based teaching (90-180 min each) were implemented in the experimental group. Questionnaires used for measuring students' motivation and engagement in science learning were administered as pre- and post-tests. In addition, eight to ten male and female students from both experimental and control groups, as well as two instructors were interviewed four times throughout the semester. Quantitative data were analyzed with t test and the interview data were fully transcribed and coded. Results show that male and female students under intervention expected to do more experiments because it improved their understanding. Male and female students under intervention also used more learning strategies. However, males benefited more than females from the intervention in regard to their motivation and engagement in learning science. Males improved more in motivational constructs, recognized the value of learning science, and increased their cognitive, behavioral, and emotional engagement because what they learned applied to real life. In contrast, females had higher exam anxiety and lower cognitive engagement due to mathematics fear, stronger sense of pride in class, and caring too much about the right answers.