Several studies have shown that student-centered instructional methods integrated with technology are effective in learning science, including biology. Therefore, this study aimed to investigate the effect of the 7E learning cycle model integrated with computer animation on students‘ conceptual understanding, misconceptions, science process skills, and attitudes towards biology, particularly on the topic of ―food making and growth in plants‖ in Metekel secondary schools, Ethiopia. To achieve this aim, a mixed research approach was applied, using a non-equivalent pretest, multiple treatments, and a posttest control group quasi experimental research design. The study was carried out in three purposively selected schools , each with one class and teacher assigned as treatment group 1(TG1), treatment group 2(TG2), and comparison group (CG) randomly. 51, 48, and 52 students were involved in TG1, TG2, and CG, respectively. The groups were taught about food making and plant growth for two months using the 7E learning cycle model integrated with computer animation (7E LCM with CA), the 7E learning cycle model alone (7E LCM), and conventional instructional methods (CIM), respectively. A two-tier conceptual understanding multiple-choice test, the Attitude Scale toward Biology, the Science Process Skill Test, and semi-structured interviews were used as the research instruments. The ANOVA analysis revealed that there were no significant differences in conceptual understanding, misconceptions, attitude towards biology, and science process skill before the intervention among the groups and genders. However, a MANOVA result revealed significant differences in mean scores between groups in conceptual understanding, misconceptions, attitude towards biology, and science process skills after the intervention. Specifically, TG 1 students had better scores than TG 2 and CG in conceptual understanding, misconceptions, attitude towards biology, and science process after the intervention. The results of the interview also confirmed these findings in relation to conceptual understanding and misconceptions. However, the MANOVA result indicated that there was no statistically significant mean difference between male and female students in conceptual understanding, misconceptions, attitude towards biology, and science process after the intervention. The study concluded that the 7E LCM integrated with CA is a more effective instructional approach for improving students‘ conceptual understanding, attitude towards biology and science process skills, and minimizing misconceptions than other instructional methods. Therefore, it is recommended that educational policymakers, curriculum planners, teachers, and other stakeholders consider implementing the 7E learning model integrated with computer animation instruction to improve students‘ biology conceptual understanding, attitude toward biology and science process skills, and minimize misconceptions