In recent years, the synthesis of materials in lower dimensions, like two-dimensional (2D) or ultrathin crystals, with distinctive characteristics has attracted substantial scientific attention. The mixed transition metal oxides (MTMOs) nanomaterials are the promising group of materials, which have been extensively utilized for various potential applications. Most of the MTMOs were explored as three-dimensional (3D) nanospheres, nanoparticles, one-dimensional (1D) nanorods, and nanotubes. However, these materials are not well explored in 2D morphology because of the difficulties in removing tightly woven thin oxide layers or exfoliations of 2D oxide layers, which hinder the exfoliation of beneficial features of MTMO. Here, through the exfoliation via Li ion intercalation and subsequent oxidation of CeVS under hydrothermal condition, we have demonstrated a novel synthetic route for the fabrication of 2D ultrathin CeVO NS. The as-synthesized CeVO NS exhibit adequate stability and activity in a harsh reaction environment, which gives excellent peroxidase-mimicking activity with a value of 0.04 mM, noticeably better than natural peroxidase and previously reported CeVO nanoparticles. We have also used this enzyme mimic activity for the efficient detection of biomolecules like glutathione with a LOD of 53 nM.