Hydrogen peroxide is regarded as a significant diagnostic marker involving a variety of pathological effects in organisms. A smart material with a colorimetric H2O2-responsive is desired and challenging to produce. Here, a colorimetric H2O2-responsive hydrogel was prepared by introducing a phenolphthalein-based cross-linking agent, which has been carefully characterized by solid-state NMR and SEM observations. Owing to the B-C linkage in the as-formed hydrogel, the colorless hydrogel gradually turns into fuchsia in the presence of H2O2 in alkalescence environment. Then the hydrogel was explored as a H2O2-responsive drug delivery system by using halloysite (Hal) as carries. The addition of Hals effectively improves the mechanical properties and reduces the initial burst release of hydrogel. The drug release behavior exhibits a typical H2O2-responsive character. The colorimetric feature can be used to estimate both H2O2 level and drug release rate.