<p>Cellulose is an abundant biopolymer found in plant cell walls, in which it provides structural support to maintain cell integrity. During biosynthesis, aligned cellulose chains aggregate and form crystals — with a cellobiose unit repeatedly packed in 3D — which can be engineered at the molecular level to achieve functionalities such as ion conductance and thermal transport. For example, swelling the cellulose chains in an alkaline environment and coordinating them with transition metal ions, such as Cu²⁺, can be used to create porous cellulose materials with directional ion transport and antimicrobial properties called nanochannels. In this Review, we explore how molecular engineering of the cellulose crystal structure can be utilized to impart new functionality and expanded applications, such as thermoelectric materials for low-grade heat harvesting, ion conductors for aqueous applications, solid-state battery electrolytes and antimicrobial textiles. Additionally, we discuss how this design principle can be leveraged in other natural materials, such as chitin derived from fishery by-products. Overall, molecular engineering, closely related to the top-down processing method, can serve as a potential approach to convert biomass into value-added products.</p>