Artificial glutathione peroxidase (GPx) model 2, 2'-ditellurobis(2-deoxy-beta-cyclodextrin) (2-TeCD) which has the desirable properties exhibited high substrate specificity and remarkably catalytic efficiency when 3-carboxy-4-nitrobenzenethiol (ArSH) was used as a preferential thiol substrate. The complexation of ArSH with beta-cyclodextrin was investigated through UV spectral titrations, fluorescence spectroscopy, 1H NMR and molecular simulation, and these results indicated that ArSH fits well to the size of the cavity of beta-cyclodextrin. Furthermore, 2-TeCD was found to catalyze the reduction of cumene peroxide (CuOOH) by ArSH 200,000-fold more efficiently than diphenyl diselenide (PhSeSePh). Its steady-state kinetics was studied and the second rate constant kmax/KArSH was found to be 1.05 x 10(7) M(-1) min(-1) and similar to that of natural GPx. Moreover, the kinetic data revealed that the catalytic efficiency of 2-TeCD depended strongly upon the competitive recognition of both substrates for 2-TeCD. The catalytic mechanism of 2-TeCD catalysis agreed well with a ping-pong mechanism, in analogy with natural GPx, and might exert its thiol peroxidase activity via tellurol, tellurenic acid, and tellurosulfide.