Abstract <p>Heterocyclic frameworks containing nitrogen, oxygen, and sulfur atoms play a crucial role in modern drug discovery because of their structural diversity and wide range of pharmacological activities. Among these heterocycles, 1,3,4-oxadiazole derivatives have attracted significant attention due to their chemical stability, favorable physicochemical properties, and ability to interact with various biological targets. In the present study, a series of phenyl-substituted bis-1,3,4-oxadiazole thioacetamide derivatives were designed and evaluated for their antimicrobial potential along with in silico ADME analysis. These molecules contain two oxadiazole rings connected through a thioacetamide linker, providing a combination of aromaticity, electron-deficient heterocycles, and sulfur-containing functionality that may enhance biological interactions. The synthesized derivatives were tested against selected gram-positive, gram-negative, and fungal strains, where several compounds exhibited notable antimicrobial activity. Structure–activity analysis indicated that the nature of substituents on the phenyl ring influenced the biological response. Furthermore, ADME predictions suggested acceptable pharmacokinetic properties, including good absorption potential, metabolic stability, and compliance with commonly used drug-likeness criteria. Overall, the results highlight that bis-1,3,4-oxadiazole thioacetamide derivatives represent promising scaffolds for the development of new antimicrobial agents. This research contributes to the United Nations Sustainable Development Goal (SDG 3: Good Health and Well-Being) by supporting the discovery of new antimicrobial agents to address microbial infections and emerging drug resistance.</p>