Expanded PowerPoint instruction is a teaching approach through slide show presentations. This study is concerned about enhancing the academic performance and learning interest of Grade 10 students in biology. This was conducted at Siocon National High School, Siocon Compostela, Compostela Valley for School Year 2016 – 2017. The data were obtained using a quasi-experimental nonequivalence pretest-posttest research design. A validated researcher-made achievement test was administered as the pretest to both groups before the treatment was given for two weeks and was subjected afterward to the post-test. The data were analyzed using Mean, Standard Deviation, and ANCOVA at 0.05 level of significance. The findings show that students’ academic performance with the Expanded PowerPoint presentation is far better than those students taught with a conventional approach using the K to 12 Science Module. This likewise reveals that the students taught with expanded PowerPoint presentations had a very high level of interest in learning the five biology topics covered in this study. It was recommended that Teachers should be encouraged to attend training and seminar workshops on the making of expanded PowerPoint presentations.