Nicotinamide adenine dinucleotide (NAD) is a critical regulator of metabolic networks, and declining levels of its oxidized form, NAD, are closely associated with numerous diseases. While supplementing cells with precursors needed for NAD synthesis has shown poor efficacy in combatting NAD decline, an alternative strategy is the development of synthetic materials that catalyze the oxidation of NADH into NAD, thereby taking over the natural role of the NADH oxidase (NOX) present in bacteria. Herein, we discovered that metal-nitrogen-doped graphene (MNGR) materials can catalyze the oxidation of NADH into NAD. Among MNGR materials with different transition metals, Fe-, Co-, and Cu-NGR displayed strong catalytic activity combined with >80% conversion of NADH into NAD, similar specificity to NOX for abstracting hydrogen from the pyridine ring of nicotinamide, and higher selectivity than 51 other nanomaterials. The NOX-like activity of FeNGR functioned well in diverse cell lines. As a proof of concept of the in vivo application, we showed that FeNGR could specifically target the liver and remedy the metabolic flux anomaly in obesity mice with NAD-deficient cells. Overall, our study provides a distinct insight for exploration of drug candidates by design of synthetic materials to mimic the functions of unique enzymes (e.g., NOX) in bacteria.