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A colorimetric method combining WSe2 nanosheets with peroxidase-like activity and xanthine oxidase (XAO) was developed for xanthine detection. XAO catalyzes xanthine oxidation and thereby induces H2O2 production. WSe2 nanosheets can catalyze the oxidization of 3,3′,5,5′-tetramethylbenzidine (TMB) by H2O2 and produce a blue oxidation product of TMB (oxTMB). Under optimal conditions, the colorimetric method showed a linear response for xanthine detection in a range of 0.01–0.5 mM. The limit of detection was 4.37 μM. The recovery rate from spiked serum samples was 95.5%–115.5%. Therefore, our strategy provides new opportunities for the detection of xanthine and evaluation of health care. [ABSTRACT FROM AUTHOR]