As a series of attractive nanomaterials, nanozymes with great catalytic activity and specificity are well developed in the field of biosensors. Although promising, the lack of appropriate structural design strategy and limitation of sensing performance in the clinical samples remain challenging for the practical application of nanozymes. Herein, a novel copper silicate nanozyme (CSHSs-Ar) with enhanced peroxidase-like catalytic activity is synthesized through a facile in situ valence-engineered approach. After the optimization of synthesis, the resultant CSHSs-Ar nanozymes containing nearly 60% of Cu hold a higher peroxidase-like catalytic activity and a better catalytic specificity than the other two derivatives (CSHSs and CSHSs-air). Theoretical calculations also demonstrate that CSHSs-Ar nanozymes are more beneficial toward the activation of HO compared with CSHSs and CSHSs-air. On this basis, the well-developed CSHSs-Ar nanozyme-involved system is employed as an efficient colorimetric sensor for the detection of volatile sulfur compounds (VSCs) and prediction for periodontitis. Moreover, several visual molecular logic gates are explored as a proof of concept to the application of CSHSs-Ar nanozymes with superior peroxidase-like catalytic activity. This study not only provides guidance for the development of novel nanozymes, but also broadens the biomedical application potential of nanozymes including the detection of oral diseases.