<p>Smart responsive polymers play a pivotal role in material development and biomedical applications. Focusing on the low critical solution temperature (LCST) property of thermally responsive N-isopropylacrylamide (NIPAM) hydrogel, this study introduces a zwitterionic monomer, sulfobetaine methacrylate (SBMA), to fine-tune the swelling properties and thermo/solvent responsive behaviors of P(NIPAM-SBMA) hydrogels. The innovative incorporation of SBMA imparts these hydrogels with superior swelling characteristics and broad temperature-responsive ranges, evidenced by a unique biphasic response to NIPAM content variation. A significant finding is the suppression of the cononsolvency effect in PNIPAM, traditionally observed in mixed methanol or ethanol-water solvents, upon SBMA integration. Molecular simulation was employed to analyze the affinity between various components, as well as the water adsorption capacities of NIPAM and SBMA units in copolymer hydrogels with different NIPAM/SBMA mass ratios. Combined with experimental results, the core mechanisms governing the swelling and cononsolvency behaviors of P(NIPAM-SBMA) hydrogels were explored. This work not only provides insights into the role of SBMA’s zwitterionic nature in stabilizing the polymer network against solvent-induced collapse, but also paves the way for the design of stimuli-responsive hydrogels with tailored properties for advanced biomedical and material applications.</p> Graphical abstract <p></p>