Constitutional dynamic networks (CDNs) attract interest as signal-triggered reconfigurable systems mimicking natural networks. The application of CDNs to control material properties is, however, a major challenge. Here we report on the design of a CDN consisting of four toehold-modified constituents, two of which act as bidentate units for chain-elongating, while the other two form a tetradentate structure acting as a crosslinking unit. Their hybridization yields a hydrogel of medium stiffness controlled by the balance between bidentate and tetradentate units. Stabilization of the tetradentate constituent by an auxiliary effector up-regulates the crosslinking unit, yielding a high-stiffness hydrogel. Conversely, stabilization of one of the bidentate constituents by an orthogonal effector enriches the chain-elongation units leading to a low-stiffness hydrogel. Using appropriate counter effectors, the hydrogels are reversibly switched across low-, medium- and high-stiffness states. The hydrogels are used to develop self-healing and controlled drug-release matrices and functional materials for operating biocatalytic cascades.