The 1,3,4-thiadiazole nucleus has attracted the attention of medicinal chemists during the last decades due to its multiple pharmacological activities, such as antiviral, anticancer, antibacterial, and anticonvulsant activity. This scaffold's structural alteration could aid in developing novel therapeutically effective drugs. Incorporating this adaptable pharmacophore into a well-established medicinally active molecule results in hybrid molecules with diverse pharmacological effects. These encouraging reports suggested that this privileged skeleton should be thoroughly researched for medicinal purposes. Hence, an attempt has been made in this compilation to review the structure-activity relationships of numerous thiadiazole derivatives reported in the literature with varied pharmacological properties. This review provides an up-to-date explanation of the various synthesized 1,3,4- thiadiazole analogs and their pharmacological importance.