Bacterial toxin-mediated diarrheal disease is a major cause of morbidity and mortality worldwide. In this work we designed an on-bead library of protease-resistant, acid-stable peptoid molecules and screened for high affinity binding of cholera toxin. From 100 000 compounds, we discovered a single sequence of residues that can bind and retain cholera toxin at high affinity when immobilized on a solid-phase particle. Furthermore, we demonstrate that these peptoid-displaying particles can sequester active cholera toxin from cell culture media sufficient to protect intestinal cells. We foresee this work as contributory to a potential adjunct therapeutic strategy against cholera infections and other toxin-mediated diseases.