Nanozymes, as a class of synthetic enzymes, have the characteristics of abundant raw materials and powerful environmental adaptability, potentially serving as substitutes for natural enzymes. Herein, the MoS2 nanosheets were anchored on the surface of alkali activated halloysite nanotubes by utilizing a facile hydrothermal process, resulting in the formation of MoS2@halloysite (MoS2@HNTs) core-shell nanocomposites. The catalytic effect of material on peroxidase under the mechanical stress of applied ultrasonic vibration was systematically investigated with 3,3′,5,5′-tetramethylbenzidine (TMB) as the substrate for chromogenic reaction. The results demonstrated that the established piezoelectric polarization effect generated by MoS2 with asymmetric crystal structure under mechanical force can promote the in-situ coloration of TMB. Concretely, MoS2@HNTs possessing higher Michaels constant (3.42 mmol L-1) and reaction velocity (3.16 × 10–6 mol L-1 min-1) exhibited enhanced peroxidase-like activity compared to pristine MoS2 microspheres. This may be attributed to the fact that halloysite dispersed the MoS2 nanosheets, exposing more reactive sites, and the nanocomposites produced more pronounced structural deformation under mechanical stress. The detailed experiments and theoretical calculation have elucidated the structure-activity relationship and microscopic mechanism among the microstructures, piezoelectric polarization effects and peroxidase catalytic effects of materials. This work provides an advanced prototype for the research of environmental responsive enzyme-like catalytic effects of mineral-based nanozymes with the regulation of external environmental factors.