Glutathione (γ-glu-cys-gly) is a tripeptide involved as a reducing agent in many biological systems. It is a very attractive ligand for preparing water-soluble nanoparticles for biological applications because of its favorable properties such as the presence of thiol functional group, water-solubility, biological compatibility, and the potential for further functionalization. An example of a biological application is the labeling of biomolecules for electron microscopy analysis. We have synthesized several derivatives of glutathione, including glutathione hydrazide, nickel nitrilotriacetic acid functionalized glutathione, and S-substituted glutathione ligands. These derivatives were used as ligands to prepare size-controllable gold nanoparticles for site-specific labeling of proteins such as histidine-tagged proteins, glycoproteins, and glutathione S-transferase-tagged proteins. The synthesis and characterization of the gold nanoparticles as well as the results of the labeling experiments are presented.