Nanozyme with the merit of excellent and adjustable catalytic activity, outstanding stability and low cost is a promising alternative for natural enzymes widely applied in a variety of fields. In the present study, a new two-dimensional cobalt-based MOF nanocomposite designated as MVCM@8-CD was synthesized. Combined with the strategies of increasing the ratio of Co(III)/Co(II) and modifying with small molecule 8-cyclodextrin (8-CD), MVCM@8-CD displayed remarkably enhanced oxidase-mimicking activity, which was attributed to synergistic effect from large surface area of two dimensional Co-MOF nanosheet, numerous exposed active sites, high -proportioned trivalence of cobalt and regulating action of 8-cyclodextrin. The addition of aminophenol iso-mers inhibited the catalytic oxidation process, resulting in different color change of the solution and UV-Vis absorption behaviors, based on which a sensitive ratiometric colorimetry for m-aminophenol (m-Ap) and a simple colorimetric p-aminophenol (p-Ap) detection method were developed with the detection limit of 0.16 mu M and 1.01 mu M, respectively. This method realized the colorimetric differentiation of aminophenol isomers, which provided a simple, accurate and low-cost approach for visual discrimination without complicated instrument and procedure, especially appropriate for on-site detection.