This study examined the effects of 3D model of human digestive system (3-DMHDS) on senior secondary school students’ performance in Human digestive system in Ilorin, Kwara State, Nigeria. The research adopted a post-test, control group, non-randomized, and non-equivalent quasi-experimental research design. Two intact classes from two secondary schools were randomly sampled based on institutional ownership. The instruments used were Lesson Note (LN), Biology Performance Test (BPT) for data gathering, and 3D-model of human digestive system (3-DMHDS) as the treatment instrument. The reliability coefficient of BPT was determined using the Pearson product-moment correlation and was found to be 0.84. Three research questions and three research hypotheses were formulated for the study. The mean score was used to answer the research questions while an independent sampled t-test at 0.05 level of significant was used to test the hypotheses. Findings show that 3-DMHDS significantly influence the understanding of the human digestive system among students irrespective of their gender and institutional ownership. It was recommended among others that Biology teachers and students should be motivated to use the 3D model for the teaching and learning of the human digestive system among other biology topics.