The liquid−liquid interface offers a confined space to control the growth of nanomaterials. In this study, Fe(II) (water phase) induced Meso-tetra (4-carboxyphenyl) porphyrin (H 2 TCPP) (CHCl 3 , organic phase) into nanoaggregates (Fe-TCPP) in the liquid−liquid interface. By tuning the ratio of DMF in organic solvents, Fe(II) induced H 2 TCPP into two nanoaggregates (Fe-TCPP-1 and Fe-TCPP-2) with different morphologies via coordination interaction occurring at the water−CHCl 3 interface. Interestingly, the Fe-TCPP nanoaggregates possess dual enzyme-like activity (peroxidase-like and oxidase-like activity). In particular, both Fe-TCPP-1 and Fe-TCPP-2 demonstrate a peroxidase-/oxidase-like activity under visible light irradiation that is higher than that in the dark. Comparatively, Fe-TCPP-2 exhibits enhanced peroxide-like (POD) activity together with oxidase-like (OXD) activity compared with that of Fe-TCPP-1 under the corresponding similar conditions. The excellent enzyme mimic activity of Fe-TCPP nanozymes is ascribed to the generated hydroxyl radicals (•OH) and superoxide anions (O 2
•−). Remarkably, the catalytic activity of Fe-TCPP-2 remains more than 90% even in the higher temperature range of 35−40 °C, which is significant for biological detection under physiological conditions. Based on the outstanding dual enzyme-like activity of Fe-TCPP-2, a colorimetric sensing platform for methimazole (an antithyroid medicine) has been developed, demonstrating a linear detection range of 10−100 μM and a detection limit of 4.44 μM.