<p class="ql-align-justify">Lately, much interest has been focused on the chemistry and the biological activity of fused heterocyclic compounds carrying nitrogen atoms because of their utility in various applications, and over the years N-bridged heterocyclic systems derived from 1,2,4-triazoles attracted the interest of researchers owing to the hopeful promise of their pharmacological activities such as antimicrobial, antifungal, molluscicidal, nematicidal, analgesic, anti-inflammatory, anticancer, phosphodiesterase 4 inhibitor, acetylcholinesterase, butyrylcholinesterases and alkaline phosphatase inhibitor. The fused ring of triazole and thiadiazines, named as triazolothiadiazines, represents a specific and important class of N-bridged heterocycles with their remarkable and wide range of biological activity and there are not enough studies that include the current developments associated with the new synthesis techniques and novel biological evaluation results of 1,2,4-triazolo[3,4-b][1,3,4] thiadiazine derivatives. In an attempt to overcome this deficiency in the literature, we deeply researched the literature and formed a review study about the discovery, synthesis and activity evaluation of new compounds bearing 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine moiety within the years of 1996-2019. We aimed to provide scientists with a wide data resource about 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine derivatives, thus helping them perform a more organized and fertile drug discovery operation during their experimental studies.