Tough hydrogels with high mechanical properties and multi-responsiveness have attracted increasing attention in recent decades. Herein, we report a series of tough semi-interpenetrating hydrogels (poly(N-acryloyl-2-glycine)/polyvinyl alcohol hydrogels, PACG/PVA hydrogels, i.e., PAP hydrogels) comprised of natural amino acid-derived polymers PACG within physical crosslinked PVA. The PAP hydrogels demonstrated tunable mechanical properties, with tensile breaking stress (σb), breaking strain (ϵb), Young's modulus (E) and toughness (Wb) of 0.14-1.38 MPa, 420-530%, 15-106 kPa and 21-308 kJ m-3, respectively. Based on the ionizable side chains containing amino and carboxyl groups of PACG, the PAP hydrogels exhibited a significant response to salt and pH as well as self-healing, self-rolling, and reconstruction ability. Thus, the obtained hydrogels can act as promising candidates in soft actuators, flexible sensors, etc.