<p> A label-free colorimetric biosensor based on Au@Ag@AgCl core-shell nanomaterials has been developed. The biosensor operated through a unique mechanism where Au@Ag@AgCl nanoparticles were progressively etched by ammonia produced during urease-catalyzed urea decomposition. This etching process induced a distinct color transition of the colloidal solution from orange to pink and ultimately to red, enabling quantitative determination of urease concentration. The multi-core-shell design of Au@Ag@AgCl provided highly enriched color gradients and significantly enhanced visual resolution, achieving a detection limit of 0.147 U/mL, which was 85 times lower than that of the commercial urease test strips. Notably, the assay required no complex surface modifications or separation procedures, offering high operational simplicity which could be accomplished within 15&#xa0;min. All these advantages greatly facilitated in-situ and in-time detection of urease. Finally, this assay was applied to the detection of simulated saliva samples with recoveries ranging from 104.4% to 123.0%, thereby validating its robust anti-interference capability and potential application in practice. Thus, the proposed Au@Ag@AgCl core-shell nanostructure-based label-free biosensor might provide a rapid, quantitative, and user-friendly alternative approach for monitoring <i>Heliobacter pylori</i> infection.</p> Graphical Abstract <p></p>