Dynamic regulation of intermolecular interactions is essential for the creation of dynamic supramolecular materials with lifelike self-regulating functions. Yet specific ion effect, which is known to possess potent effect on intermolecular interactions, has remained unexplored for such a purpose. Here, we demonstrate our access to dynamic self-assembly of supramolecular hydrogels by orchestrating the Hofmeister effect through a simple enzymatic reaction. The involved gelators containing carboxylate moieties self-assemble into hydrogel (Gel1) at acidic pH and dissolve at basic pH. We surprisingly find that the dissolved gelators at basic pH can be driven to self-assemble into hydrogel (Gel2) by kosmotropic ions through the disruption of gelator–water interactions. By coupling to the enzymatic hydrolysis of urea, Gel1 gradually disintegrates over time because of the production of basic NH3. However, interestingly, with the accumulation of kosmotropic ions, NH4+ and CO32−, the dissolved gelators are driven to self-assemble into Gel2, realizing a self-regulating gel–sol–gel transition process. The transition rate and stiffness of Gel2 are tunable by adjusting the concentrations of urea or urease. This work may shed light on the creation of lifelike self-regulating supramolecular materials using Hofmeister effect for many enticing applications such as ion-programmed biosensing and drug delivery.