This study was focused on the synthesis and antiparasitic activity assessment of nucleobase-tethered trithiolato-bridged dinuclear ruthenium(II)-arene compounds, aiming at exploiting the parasite auxotrophies and metabolic peculiarities regarding this type of metabolites. Diverse types of structures and synthetic strategies were proposed and evaluated, leading to the isolation of 17 diruthenium moietynucleobase hybrid molecules. To appraise the nucleobase-conjugate strategy, 6 derivatives presenting other type of anchored molecules were also obtained and tested. CuAAC reactions proved to be a useful method for the functionalization of trithiolato diruthenium compounds with various substrates including nucleobase derivatives. The organometallic fragment could be used both as alkyne and azide group bearing partner and allowed the isolation of 19 new click conjugates. This strategy can be extended to develop other thiolato-bridged ruthenium(II)-arene hybrids in a convenient manner and can eventually be used to construct larger libraries of compounds.