New trehalose-containing hydrogels and the first hydrogels cross-linked by mono- or disaccharide acetals that are degradable in acidic medium were designed and synthesized. The cross-linking agent was obtained in acetalization reaction of trehalose with x-allyloxybenzaldehyde in which diallyl compounds were formed and used afterward in free radical copolymerization with N-isopropylacrylamide (NIPAAm) to provide thermo-sensitive hydrogels. Depending on the trehalose diacetal isomer and solvent system used in copolymerization, as well the degree of network cross-linking, these hydrogels differed in morphology, swelling and deswelling behavior and time of degradation. Compared with conventional PNIPAAm hydrogels they are degradable what makes them good materials for biomedical applications. Display omitted •Thermo-sensitive hydrogels cross-linked by trehalose diacetals were synthesized.•Trehalose diacetal cross-linker provide acid-degradability to hydrogels.•Hydrogels differed in morphology swelling ratio and degradation time were obtained.