Reaction of 2-amino-1,3,4-thiadiazole (1) with chloroacetyl chloride afforded the chloroacetamide 2 which used as starting compound for the synthesis of 2-thiocyanatoacetamide 3 and N-(1,3,4-thiadiazol-2-yl) acetamides 5–9 via reaction of 1 with various reagents. Treatment of 9 with 4-(piperidin-1-yl)benzaldehyde or DMF-DMA afforded the arylidenes 10 and 11, respectively. Cyclization of the later compound with hydrazine hydrate gave the pyrazole derivative 12. Furthermore, coupling of 9 with 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-diazonium chloride afforded hydrazone derivative 13, which cyclized in acetic acid to afford 1,2,4-triazine derivative 14. Moreover, 1,3,4-thiadiazoles 15, 19, 22, and 23 were achieved via reaction of 1 with different nucleophiles. Finally, 1-phenyl-1H-pyrazol-5(4H)-one when subjected to react either with 15 or with diazonium salt of 1 afforded pyrazole derivative 16 or bis-1,3,4-thiadiazole derivative 18, respectively. Some of these compounds were screened for their cytotoxicity and antioxidant activities which showed promising results.