A series of pH-dependent thermo-sensitive hydrogels for oral insulin delivery is designed and synthesized. In contrast to normal pH- and thermo-sensitive hydrogels, the release of oral insulin from them is mainly controlled by the adjustable swelling ratios in gastric and intestinal juice with their variable pH sensitivity. The release behavior of loaded insulin depends on the swelling/shrinking transition because of the changing LCST at different pH values. The hydrogels presented are composed of PNIPAAm chains and PMAA segments and are prepared with the biodegradable acryloyl-poly(ϵ-caprolactone)-2-hydroxylethyl methacrylate as a crosslinker. The biodegradation rates of the hydrogels are directly related to their PMAA content. In vitro release of insulin from the hydrogels is investigated and the release profiles indicate that the smart hydrogels are of great promise in pH–temperature oral insulin delivery systems.