There is an urgent need to discover and develop new drugs to combat parasitic diseases as Chagas disease (Trypanosoma cruzi), Sleeping sickness (Trypanosoma brucei) and Leishmaniasis (Leishmania ssp). These diseases are considered among the thirteen most unattended diseases worldwide according to the WHO. In the present work, the synthesis of 14 arylsubstituted imidazoles and its molecular docking onto sterol 14α-demethylase (CYP51) was executed. In addition, the compounds, antiprotozoal activity against T. brucei, T. cruzi, Tb. rhod and L.inf was evaluated. In vitro antiparasitic results of the arylsubstituted imidazoles against T. brucei, T. cruzi, Tb. rhod, L.inf indicated that all samples from arylsubstituted imidazole compounds presented interesting antiparasitic activity to various extent. The ligands 5a, 5c, 5e, 5f, 5g, 5i and 5j exhibited strong activity against T. brucei, T. cruzi, Tb. rhod and L.inf with IC50 values ranging from 0.88 to 4.98 μM. Most samples were cytotoxic against MRC-5 cell lines (1.17 < CC50 < 52.03 μM) and only ligand 5c showed a good selectivity against all tested parasites. According to the results of the molecular docking, the aromatic substituents in positions 1, 4 and 5 have mainly stabilizing hydrophobic interactions with the enzyme matrix, while the oxygen from NO2, SO3H and OH groups interacts with the Fe2+ ion of the Heme group.