Understanding the ice recrystallization inhibition (IRI) mechanism is of fundamental importance for the rational design of novel antifreeze protein mimetics and reducing IR-related damage. In this communication, using quantitive experimental methods and molecular dynamics simulations we demonstrate that zwitterionic poly(carboxybetaine methacrylate) (PCBMA) can serve as a novel IRI-active substance. This work unravels the atomic-level details of the IRI mechanism of zwitterionic antifreeze protein mimetics and provides insight into the development of next-generation antifreeze protein mimetics.