This paper describes a study conducted in the context of chemistry education reforms in Israel. The study examined a new biochemistry learning unit that was developed to promote in-depth understanding of 3D structures and functions of proteins and nucleic acids. Our goal was to examine whether, and to what extent teaching and learning via model-based learning and animations of biomolecules affect students’ chemical understanding. Applying the mixed methods research paradigm, pre- and post-questionnaires as well as class-observations were employed in the collection, analysis, and interpretation of data. The research population included 175 grade twelve students, divided into three research groups: (a) hands-on exploration of animations, (b) teacher’s demonstrations of animations, (c) traditional learning using textbooks. Findings indicated that the integration of model-based learning and 3D animations enhanced students’ understanding of proteins’ structure and function and their ability to transfer across different levels of chemistry understanding. Findings also indicated that teachers’ demonstrations of animations may enhance students’ ‘knowledge’—a low order thinking skill; however, in order to enhance higher levels of thinking, students should be able to explore 3D animations on their own. Applying constructivist and interpretative analysis of the data, three themes were raised, corresponding to cognitive, affective, and social aspects of learning while exploring web-based models and animations.