Tough hydrogels with high mechanical properties and multi-responsiveness have been attracted increasing attention in decades. Herein, we reported a series of tough semi-interpenetrating hydrogels (poly (N-acryloyl-2-glycine)/ polyvinyl alcohol hydrogels, PACG/PVA hydrogels, i.e., PAP hydrogels) comprising natural amino acid-derived polymers PACG within the physical crosslinked PVA. PAP hydrogels demonstrated tunable mechanical properties, with tensile breaking stress (σb), breaking strain (εb), Young's modulus (E) and Toughness (Wb) being 0.14-1.38 MPa, 420-530%, 15-106 kPa and 21-308 kJ/m3, respectively. Based on the ionizable side chains containing amino and carboxyl groups of PACG, PAP hydrogels exhibited significant responsive to salt and pH as well as the ability of self-healing, self-rolling, and reconstruction. The obtained hydrogels can be acted as promising candidates in soft actuators, flexible sensors, etc.