We describe in the manuscript reductive glutathione (GSH)-responsive molecular release using polyhedral oligomeric silsesquioxane (POSS) network polymers. A series of the POSS network polymers with the different crosslinking ratios containing disulfide linkers were synthesized, and molecular encapsulation by the polymers was executed. We found that the POSS polymers encapsulated the molecules in aqueous solutions. On the contrary, the reduced polymers hardly retained the guest molecules. By using the change of the encapsulation ability of the polymers via reduction, we demonstrated that the dye-loaded network polymers released the encapsulated molecules. Finally, we were able to detect GSH with intercellular concentration by the increase of the intensity of fluorescence emission.