Hemoglobin-based oxygen carriers (HBOCs) offer a promising alternative to conventional blood transfusions in emergency scenarios. However, achieving optimal stability, functionality, and biocompatibility in HBOCs remains a significant challenge. In this study, we employed a HBOC formulation consisting of hemoglobin (Hb) encapsulated within zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs). These NPs were subsequently coated with metal phenolic networks (MPNs) and polyethylene glycol (PEG) to impart antioxidant properties and enhance their stability and biocompatibility. Hb-loaded ZIF-8 NPs were synthesized using a rapid, environmentally friendly protocol and exhibited desirable properties, including an average size of approximately 150 nm, a negative surface charge (zeta potential of -14 mV), high encapsulation efficiency (approximately 65%), and substantial drug loading capacity (around 70%). The MPN coating significantly enhanced stability across various buffers and cell media and endowed the NPs with antioxidant properties. Meanwhile, the PEG layer conferred stealth properties, potentially extending circulation times