In the present study, a series of 2-amino-5-sulphanyl-1,3,4-thiadiazole derivatives were synthesized in good yields and the structure of these compounds were established by means of FT-IR, 1H/13C NMR, mass, and elemental analysis. The synthesized compounds were screened pharmacologically to evaluate their central nervous system activity. The purpose of this study was to evaluate the title compounds on Central Nervous System activity by varying the substituents in the thiadiazole scaffold. Three of the tested compounds (centrally acting agents) 2a, 2d, and 2g exhibited excellent antidepressant, anxiolytic, and anticonvulsant activity in comparison to the reference drugs.