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Nanozymes offer promising alternatives to natural enzymes due to enhanced stability, tunable activity, and cost efficiency, demonstrating therapeutic potential against tumors, infections, and inflammatory disorders. Trichinella spiralis is an important pathogen, which globally prevalent foodborne zoonotic parasite. Chemical drug is commonly used to kill T. spiralis, but there are risks of chemical abuse and drug resistance. Here, we engineered MPG(Fe), a cascade nanozyme formed by covalently conjugating glucose oxidase (GOx) to a metal-organic framework-Fe nanozyme (MOF-525(Fe)) nanozyme via PEG bridging. In vitro, MPG(Fe) depleted glucose through GOx-catalyzed conversion to gluconic acid and H₂O₂, while MOF-525(Fe) subsequently transformed H₂O₂ into cytotoxic hydroxyl radicals (•OH). This dual-action mechanism dose-dependently killed intestinal-stage adult worms and newborn larvae of T. spiralis. In mice models, intra-intestinal administration of high-dose MPG(Fe) reduced adult worm survival to 3.53% by synergizing glucose starvation with •OH-mediated oxidative damage. Critically, MPG(Fe) exhibited no tissue toxicity in uninfected mice. Our findings establish enzyme-mimetic nanozymes as a novel therapeutic platform against zoonotic helminthiases.