Introduction: The research determined the effectiveness of Peer-tutoring Instructional Strategy (PTIS) and Experiential Instructional Strategy (EIS) on Biology students' academic performance and self-efficacy in schools. Methods: The research adopted a pre-test, post-test, control group quasi-experimental research design. The data collected were analysed with the use of One-way Analysis of Covariance (ANCOVA) and Two-way Analysis of Variance (ANOVA). Results: The findings of the study indicated that there existed a significant difference in the effectiveness of PTIS, EIS, and CIS on the academic performance of Biology students in senior secondary school in (F=39.65, p=0.00) as well as the self-efficacy of Biology students (F=24.778, p=0.000). Discussion: Further analysis revealed that EIS was comparatively more effective than the other two instructional strategies in promoting self-efficacy and performance. Conclusions: The study concluded that the implementation of Experiential Instructional strategy had better effectiveness on the learning outcomes of Biology students.