Metal-organic supramolecular with well-defined nanosized molecular cavity is able to encapsulate some special guest substrates so that they have been widely applied in molecular recognition and molecular separations. In this work, a highly sensitive recognition of biological molecular γ-glutamyl-cysteinyl-glycine (GSH) was achieved with a trinuclear zinc-based metal-organic cyclohelicate fluorescence probe M-1, which was assembled with zinc ion and two tridentate (N2O) ligand with dansyl sulfonamide group and hydrogen bond site. The recognition process for GSH with M-1 was determined with 1H NMR, ESI-MS, UV-Vis and fluorescence spectra. To establish the recognition mechanism of GSH, its component amino acids (Cys, Glu, Gly) were investigated by spectroscopic titrations. The results show that the M-1 with trinuclear structure exhibits high stability in a water/DMF 1∶9 solution. UV-Vis adsorption titration revealed that a significant absorbance increase at 303 nm with the addition of GSH to the M-1 solution, but an absorbance decrease was observed at 380 nm. A sharp isobestic point was obtained at 330 nm. In addition, based on the UV-Vis adsorption titration results, ESI-MS analysis of M-1 confirmed that 1∶1 complexation stoichiometry of the host-guest behavior was obtained for GSH and the association constant (log KGSH) was calculated as 462±015. Moreover, 1H NMR titrations of M-1 upon the above amino acids revealed that the Glu residue of GSH was sent into M-1 cavity through the static interactions between the COO- groups and metal ions. In addition, it was found that the fluorescence intensity exhibits a two-fold enhancement, with the emission wavelength red-shifted from 510 to 540 nm upon the addition of GSH into M-1. Upon the addition of Cys and Glu in the solution of M-1, the luminescence intensity exhibits 04 times and 02 times enhancement, respectively, with the emission wavelength not being shifted. On the contrary, no change of the luminescence intensity was observed after adding the Gly to the solution of M-1. Based on the above analysis, it is confirmed that the joint effects of size limitation of the M-1 cavity and the hydrogen bonding interactions between Cys moiety of GSH and the amide groups sited in M-1 molecuar will generate measurable spectral changes, which lead to visualizing the highly sensitive recognition for GSH. The low detection limit was up to 30×10-6 mol·L-1.