<p>The exploitation of an extremely sensitive and reliable nanozyme based colorimetric sensor for highly sensitive detection of hydrogen peroxide (H₂O₂) in living body system is extensively carping owing to fact that it garnered a prime role in causing toxic diseases. In this work, a highly novel catalyst named as Cerium oxide (CeO₂) nanosheets (NSs) was precisely prepared by using a simple one pot hydrothermal method, thereby dowered with a strong intrinsic peroxidase like capability of catalyzing the oxidation-reaction of colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to generate a blue color reaction in the presence of H₂O₂. Hence, a sensitive visible assessment platform related to CeO₂ NSs was engineered, which not only exhibited a wider detection range of 0.01–1000 µM with R² value of 0.9998, but also perceives exceptional selectivity, tremendous cycling and long term stability. Further, the sensor also evaluates lowest detection limit (LOD) 0.29 ± 0.03 µM and quantification limit (LOQ) of 2.3 ± 0.03 µM. In addition, it also endorses impressive practicality with stronger sensitivity and favorable accuracy in serum samples. Thus, this research-work not only contributed upon CeO₂ NSs an outstanding capacity to detect H₂O₂, but also expands the realm of applications for CeO₂ NSs in the domains of environmental preservation, biomedical diagnosis and forensic sciences.</p> Graphical Abstract <p></p>