Nitrogenous heterocyclic rings are present in a wide range of drugs, natural compounds, and fine chemicals and are considered privileged scaffolds in medicinal chemistry. Seeking novel antiprotozoal drugs acting on new targets or by novel mechanisms of action, we focused on a preliminary evaluation of the potential of “linear-shaped” diaryl pyrazines. To this purpose, a two-enzyme chemoenzymatic synthesis of this heteroaromatic core was proposed. Specifically, starting from simple, commercially available aromatic aldehydes, the target pyrazines were obtained through a sequence of biocatalytic benzoin condensation, chemical oxidation, and a transaminase-mediated tandem process of transamination and cyclization. The profiles of the compounds as antiprotozoal agents were evaluated in vitro against cultures of Leishmania and Plasmodium and using the human cell line HepG2.