Crotamiton, a scabicide and antipruritic agent persistent during biological treatment processes, is frequently detected in secondary effluent. In this study, titanium dioxide (TiO2) and high-silica zeolite (HSZ-385) composites were synthesized and applied for the treatment of crotamiton in secondary effluent. Crotamiton was rapidly adsorbed by HSZ-385, and the adsorption performance of crotamiton in the secondary effluent was quite close to that in the test using ultrapure water. Even though the TiO2–zeolite composites showed lower adsorption rates than that of HSZ-385, similar crotamiton adsorption capacities were revealed using both test materials. The photocatalytic decomposition of crotamiton was significantly inhibited by the water matrix at low initial concentrations. The TiO2–zeolite composites rapidly adsorbed crotamiton from secondary effluent, and then the crotamiton was gradually decomposed under ultraviolet irradiation. Importantly, when using TiO2–zeolite composites, coexisting material in the secondary effluent did not markedly inhibit crotamiton removal at low initial crotamiton concentration. The behaviors of the main intermediates during treatment demonstrated that the main degradation intermediates of crotamiton were also captured by the composites.