Given the metabolization of xanthine into uric acid, and its relevance to diseases and food safety, it is significantly desirable to propose a rapid, sensitive, and reliable strategy to monitor the expression levels of xanthine in biological liquids. Herein, a H₂O₂-responsive colorimetric sensing system was triumphantly developed for xanthine assay by combining peroxidase-mimetic magnetic Fe nanoparticles (Fe NPs) and xanthine oxidase (XOD). XOD catalyzed xanthine oxidation to H₂O₂, which combined with Fe NPs to catalyze the oxidation of the chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB) to the oxidized form (oxTMB) along with the absorbance at 652 nm appearing and increasing. Therefore, a sensitive, rapid, and convenient colorimetric platform for H₂O₂ and xanthine sensing was successfully developed with a limit of detection (LOD) of 0.029 μM for H₂O₂ and 0.034 μM for xanthine. In general, the Fe NP nanozyme with high peroxidase-like activity features low-cost, high-performance, and ease of preparation, thus providing an efficient and sensitive sensing platform for blood xanthine monitoring as an alternative to traditional strategies.