Iso‐propanol and n‐butanol were oxidized using catalase encapsulated within monolithic polyampholyte cryogel, p(APTAC‐co‐AMPS), derived from an anionic monomer, 2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid sodium salt (AMPS), and a cationic monomer, (3‐acrylamidopropyl) trimethylammonium chloride (APTAC). Macroporous polyampholyte cryogels containing various amounts of catalase were synthesized in situ under cryo‐polymerization conditions at a molar ratio of monomers [APTAC]:[AMPS] = 75:25 mol.% in the presence of 10 mol.% cross‐linking agent, N,N‐methylenebisacrylamide (MBAA). The oxidation of alcohols was carried out inside of a monolithic macroporous sample by passing the mixture of alcohol and hydrogen peroxide through at a fixed flow‐rate. Analysis using gas–liquid chromatography and gas chromatography–mass spectrometry showed that iso‐propanol is converted to acetone at a yield of 87.6%, whereas n‐butanol is converted to butyraldehyde at a yield of 80% at 20°C and atmospheric pressure. The influence of pH, temperature, and ratios of substrate to hydrogen peroxide on the degree of conversion of iso‐propanol was evaluated. SEM images of cryogel‐encapsulated catalase before and after several cycles of oxidation of iso‐propanol show collapsing, among other alterations, in the morphology of the cryogel matrix. The oxidation mechanism of iso‐propanol and n‐butanol using cryogel‐encapsulated catalase was suggested.