<p>A highly efficient photoelectrochemical (PEC) biosensor for glutathione (GSH) assay was constructed based on the target-triggered etching of CdS@MnO₂ nanocomposites (NCs). The core–shell CdS@MnO₂ NCs were prepared by a hydrothermal method and coated on the indium tin oxide (ITO) electrode as a PEC sensing platform. The PEC sensing platform gave a near-zero PEC signal due to the excellent light absorption ability of MnO₂ nanosheet coating on the CdS nanoparticles. In the presence of GSH, the etching of MnO₂ on the CdS@MnO₂ NCs was triggered because of the unique etching reaction between MnO₂ and GSH, leading to the exposure of inner photoactive nanomaterials, i.e., CdS in this system. This inevitably causes an obvious increase in the photocurrent response, which is related to the GSH concentration. Thanks to the excellent quenching effect of MnO₂ on the PEC signal of CdS, acceptable PEC performance of CdS, and the specific interaction between GSH and MnO₂, the targets-triggered etching strategy exhibited excellent analytical performance for GSH detection with a detection limit of 0.05&#xa0;μmol/L and a linear range from 0.2 to 100&#xa0;μmol/L. The PEC biosensor has advantages such as good selectivity, excellent stability, and low background. This work contributed a fresh idea to detect GSH sensitively through the PEC sensing method.</p>