To enlarge the perspective of nanozyme, 2-dimensional Co3O4 stabilizing Rh nano composite (2D Co3O4@Rh NC) was identified and developed first by one-pot surfactant-aided oxido-reduction. By virtue of the synergetic-reinforcing oxidase activity between 2D Co3O4 substrate and Rh nano particles, the obtained 2D Co3O4@Rh NC could catalyze the oxidation of chromogenic substrate 3,3′,5,5,’-tetramethylbenzidine (TMB) to blue oxTMB with quite a low Michaelis-Menten constant (Km) of 0.018 mM and a quick vmax of 6.45 × 10–8 M s–1, expressing superior oxidase-like catalysis with a wide temperature range from 20 to 60 °C. Importantly, either bioactive urea or toxic p-aminophenol (p-Ap) could exclusively alter the existed state of oxTMB with differentiable color changes. Under the optimized conditions, 2D Co3O4@Rh NC was successfully applied for ratiometric colorimetric sensing urea and p-Ap in environmental water, soil and urine samples with low detection limits (1.1 μM for urea and 0.68 μM for p-Ap) and satisfactory recoveries (96.0–105.8%). The synergetic enhanced oxidase-like activity of 2D Co3O4@Rh NC and the different reaction mechanisms of the 2D Co3O4@Rh NC-TMB system to urea and p-Ap were investigated. Not only does the work provide an efficient way for sensing organic pollution of p-Ap, it will offer an efficient potential for diagnosing urea-related diseases on clinical medical testing in future.