Abstract <p>This study focuses on the preparation, identification, and antioxidant activity of novel substituted thiadiazole derivatives. Serval novel 2-(1<i>H-</i>benzo[d]imidazol-2-yl)acetonitrile (<b>L10</b>) compounds were created. The <b>L10</b> is reacted with three aromatic aldehydes via Knoevenagel condensation to produce acrylonitrile derivatives. The nitrile group is then cyclized by thiosemicarbazide with trifluoracetic acid as a catalyst in pure EtOH as the solvent. The new ligands include 1,3,4-thiadiazole ring derivatives (E)-5-(1-(1<i>H-</i>benzo[d]imidazol-2-yl)-2-(4-nitrophenyl)vinyl)-1,3,4-thiadiazol-2-amine (<b>L12</b>), (E)-4-(2-(5-amino-1,3,4-thiadiazol-2-yl)-2-(1<i>H</i>-benzo[d]imidazol-2-yl)vinyl)phenol (<b>L13</b>) and (E)-5-(1<i>H-</i>benzo[d]imidazol-2-yl)-2-(4-chlorophenyl)vinyl)-1,3,4-thiadiazol-2-amine (<b>L15</b>). Some of these ligands were made using the classic reflux approach, while others were created using the microwave method. The majority of the produced compounds were characterized using spectroscopic methods (FTIR, ¹H NMR, and ¹³C NMR). The efficiency of the two compounds (<b>L11</b> and <b>L13</b>) as antioxidants was also investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Antioxidant activity tests for these compounds revealed good results.</p>