Type 1 diabetes mellitus (T1DM) are characterized by blood glucose elevation with pancreatic β cells deficiency. As a safe alternative to frequent subcutaneous insulin injection, pancreatic β cell transplantation provides a promising therapeutic option for blood glucose control in T1DM. However, pancreatic β cell transplantation faces intractable challenges of the poor viability and severe host immune rejection. Therefore, a novel approach capable of improving the poor oxygen/nutrients supply and severe host immune rejection is highly desired. Herein, a novel biohybrid artificial pancreas, presenting glucose-dependent insulin release behavior, is constructed via pancreatic β cells encapsulating in a hydrogel scaffold. The hydrogel scaffold is made of the commixture of sodium alginate (SA), chitosan (CS) and sulfated bacterial cellulose (SBC). The biocompatible three-dimensional (3D) hydrogels protected pancreatic β cells from immune response but also allowed the exchange of nutrients and insulin. As a result of the synergistic effect, the biohybrid artificial pancreas can reverse the hyperglycemia and achieve sustained glycemic control for at least 30 days in diabetic mice. Collectively, we consider that this biohybrid artificial pancreas with an elaborate structure could provide an effective option for the treatment of type 1 diabetes.