In this study, a series of novel [1,2,4]-triazolo-[1,3,4]oxadiazole (8), [1,2,4]-triazolo-[1,3,4]oxadiazole thioethers (9a–b), [1,2,4]-triazolo-[1,3,4]oxadiazole arylidines (10a–g), and bis[1,2,4]-triazole (11) derivatives were prepared with the objective of developing better antimicrobial activity. The structures of the compounds were elucidated by spectral analysis. The newly synthesized compounds (8), (9a–b), (10a–g), and (11) were screened for their antimicrobial activity. Among all the tested compounds (10b) shows significant antibacterial activity.