In this dispensation of rapid scientific and technological advancements, significant efforts are being made to curb health-related diseases. Research discoveries have highlighted the value of heterocyclic compounds, particularly thiadiazole derivatives, due to their diverse pharmacological activities. These compounds play a crucial role in therapeutic medicine and the development of effective drugs. Thiadiazoles are five-membered heterocyclic compounds consisting of one sulfur and two nitrogen atoms. This review explores advanced synthesis techniques, including the use of heterogeneous catalysts, microwave-assisted methods, ultrasound-assisted synthesis, solvent-free processes, multicomponent reactions, copper-catalyzed aerobic oxidative annulation, intramolecular cyclization, click-chemistry supported synthesis, and alkali-promoted, transition-metal-free mediated synthesis. These methods enhance the diversity and potential applications of thiadiazole compounds. Furthermore, this study provides up-to-date information on the key pharmacological activities of thiadiazole derivatives, highlighting their potential in therapeutic medicine for drug development. The structure-activity relationship (SAR) is also discussed to better understand their interactions and safety in biological systems. This work aims to expand on the reported chemistry and pharmacological potential of the thiadiazole moiety to validate their efficacy as promising pharmacophores in drug design and development.