High thiophillicicity of the Au-nanoparticle (Au NP) surface leads to covalent attachment of D-penicillamine molecules to Au NPs to form biocompatible D-penicillamine conjugated Au NPs. The latter are highly water-dispersible, exhibit no cytotoxicity, and can readily penetrate the cell membrane to target intracellular free copper ions for selective copper detoxification in the presence of the other divalent essential metal ions including Zn(II), Fe(II), Mn(II), Ca(II), and Mg(II), thus opening up a new avenue for improving the efficacy and pharmacokinetics of D-penicillamine, an important clinical drug currently used to treat the copper overload-related diseases and disorders.