Originated from nature and used for nature is a way of sustainable development. In this work, montmorillonite (MMT), a natural two-dimensional (2D) layered mineral, the surface and interlayer of which were nano-decorated by chemical synthesis technique was applied in biological detection field. Magnetic ferrite (Co_0.5Ni_0.5Fe₂O₄) was anchored on the surface and intercalated in the interlayer of montmorillonite, which served as a competitive candidate of enzyme mimics. Cytotoxicity test toward HUVEC and Hela cells verified the good biocompatibility of Co_0.5Ni_0.5Fe₂O₄-MMT, guaranteeing its safety in biological applications. Based on the peroxidase-like activity of Co_0.5Ni_0.5Fe₂O₄-MMT, a colorimetric sensing platform for H₂O₂ was established by a facile mix-and-detect approach with the detection limit of 0.565 μM (3σ/slope). It was implied that the peroxidase-like activity of Co_0.5Ni_0.5Fe₂O₄-MMT was originated from generation of ·OH and ·O₂^– produced from catalytic decomposition process of H₂O₂. Coupled with cascaded catalytic reactions of ACh, a facile and efficient sensing platform for ACh with satisfactory anti-interference ability was established. Thus, all these remarkable features highlighted the superiority of Co_0.5Ni_0.5Fe₂O₄-MMT, and endowed it with a powerful competitiveness in the fields of environmental assessing, biosensing, and disease monitoring.