Here, we report ZIF-8-reduced graphene oxide (ZIF-8-rGO)-supported bimetallic AuPt nanoparticles (AuPtNPs) as a novel peroxidase mimic for high-sensitivity detection of HO in neutral solution. ZIF-8-graphene oxide (ZIF-8-GO) is first synthesized via a simple wet-chemistry process and subsequently immobilized with AuPtNPs via a reduction method. The resultant AuPt/ZIF-8-rGO shows enhanced peroxidase-like catalytic activity and it is applied for the electrochemical detection of HO in a wide concentration range, from 100 nM to 18 mM, with a very low detection limit of 19 nM (S/N = 3). This good electroanalytical performance of AuPt/ZIF-8-rGO is owing to the ultrasmall size and high dispersion of the AuPtNPs, the strong metal-support interaction between the AuPtNPs and ZIF-8-rGO bisupport, and the sandwich-like structure comprising porous ZIF-8 and loosely packed rGO nanosheets. The AuPt/ZIF-8-rGO is employed for the practical detection of HO in human serum samples with desirable properties. Therefore, the novel AuPt/ZIF-8-rGO is a promising nanozyme for various biotechnological and environmental applications.