Glutathione (GSH) as a biothiol is an essential peptide related to various diseases. Although multiple strategies for biothiols detection have been developed, there is increasing demand for sensors that can differentiate GSH from cysteine (Cys) and homocysteine (Hcy), owing to the similar structures and thiol groups in these amino acids. Herein, we report a novel Eu/LAPONITE (Lap)-based organic/inorganic hybrid material for selective detection of GSH via an "off-on" process. The fluorescence of Eu(DPA)@Lap-Tris can be quenched by Cu through photoinduced electron transfer (PET). The addition of GSH into the Eu(DPA)@Lap-Tris/Cu system induces the removal of Cu from Eu(DPA)@Lap-Tris and blocks PET, resulting in the recovery of fluorescence. This proposed assay demonstrates higher selectivity toward GSH than Cys and Hcy, and showed a detection limit of 162 nM within a linear range of 0.5-30 μM. Unlike other GSH selective sensors, this platform could be formed into a hydrogel while its sensitivity was maintained. The sensitive response to GSH in serum samples makes this platform an efficient tool for biological applications because of its ease of preparation, high selectivity, good biocompatibility, and low toxicity.