Zearalenone (ZEN) is a nonsteroidal estrogenic mycotoxin with widespread contamination. Inspired by lactone hydrolases, a peptide-based enzyme mimetic material for degrading ZEN was developed by combining serine, histidine and glutamate (S/H/E) catalytic triad with pro-hydrophobic self-assembling sequences and oxyanion hole site. Chitosan hybrid membranes were prepared, followed by immobilizing enzyme mimic on the membrane surface to fabricate biocatalytic membrane reactor. The membrane reactor, with good thermal stability and high catalytic activity after repeated use, can be applied to the degradation of ZEN in food. Computer simulation studies of the degradation mechanism indicated that the carbon atom on the lactone bond within ZEN molecule was susceptible to catalytic triplex attack, leading to lactone bond broken, followed by spontaneous decarboxylation to produce dihydroxyphenyl derivatives with greatly reduced binding capacity to the estrogen receptors. This kind of peptide-based enzyme mimetic material would be very promising in degrading mycotoxins in food safety field.