Tackling the escalating challenges of treating human diseases necessitates multipronged advances in both biomaterial synthesis and characterization, as well as a deeper understanding of the causes of these diseases. My dissertation addresses this urgent need by delving into two closely linked topics: the creation of novel biomaterials through a bottom-up, bio-inspired computational design approach, and the use of advanced computational techniques to unravel the complex relationship between structure, property, and functionality in biological systems. In the first topic, I pioneer advances in materials science to revolutionize healthcare with deep characterizations of the intricate interactions in silk-based soft ionic conductors and the multiscale mechanisms of silk-elastin-like proteins’ response to diverse stimuli. In the second topic, I conduct computational analyses of biological material behavior that are essential for disease prevention and treatment. I examine the denaturing mechanisms of Enterovirus 71 in the presence of potential antiviral compounds, and I investigate the molecular impact of type I collagen mutations on the bone disease, osteogenesis imperfecta. These insights not only deepen our understanding of key molecular mechanisms but also lay the groundwork for developing innovative therapeutic approaches and for the rational design of new-generation biomaterials.