In this study, we have designed and synthesized a chemosensor, isatin-based triazole-linked silanes (ITS), employing the Cu(I)-catalyzed Azide-Alkyne cycloaddition reaction (CuAAC) and the synthesized silanes has been well characterized through various analytical techniques, including FT-IR, 1H NMR, 13C NMR, and ESI-MS. The developed sensor exhibited the capability to detect Ni2+ ion in a methanol/water solution (9:1, v/v) by manifesting different absorbance changes and fluorescence. In the fluorescence mode, the addition of Ni2+ ion triggers a “Turn-OFF” response in the sensor, demonstrating an ultratrace detection limit of 2.49 × 10−7 M. Successful grafting of organosilane onto silica nanoparticles has been achieved, and these new silane-coated nanoparticles demonstrate enhanced sensing abilities for Ni2+ ions, with a detection limit of 1.56 × 10−8 M. Stoichiometric data reveals a 1:1 coordination between the sensor and Ni2+ ion. Furthermore, both the synthesized alkyne and silane underwent examination for their drug-likeness profiles, providing valuable insights.