Abstract: This invention discloses a natural polyphenols-based, multi-stage porous hydrogel sustained release drug delivery system, which relates to the field of drug delivery. It consists of the hydrogel matrix and the supramolecular filler, which is a complex of natural bio-based polymers and metal ions. The natural bio-based polymer can be natural polyphenols, dopamine or its derivatives, polysaccharide biomass, or protein biomass. The hydrogel matrix can be chitosan, carboxymethyl chitosan, sodium alginate, carboxymethyl cellulose, hyaluronic acid, collagen, gelatin, or agarose. The metal ion can be one of the cations of Al, Fe, Zn, Mn, Ni, Co, or V. By this invention, the supramolecular filler based on natural bio-based polymer can form in situ in the hydrogel, to regulate the pores of the hydrogel and interact with different drugs, thus adjusting the drug release rate.