AbstractTuberculosis remains a leading global health threat, exacerbated by the emergence of multi‐drug‐resistant strains. The search for novel therapeutic agents is critical in addressing this challenge. This review systematically summarizes the potential of oxadiazole derivatives as promising candidates in antimycobacterial drug discovery. We focus on various classes of oxadiazoles, especially 1,2,3‐oxadiazoles, 1,2,4‐oxadiazoles, and 1,2,5‐s in structure‐activity relationship studies are discussed, emphasizing the mechanisms of antimycobacterial action. Additionally, the synergistic potential of 1,2,4‐oxadiazoles in enhancing the efficacy of existing tuberculosis treatment with ethionamide is also discussed. By integrating insights from recent research, this review aims to provide a comprehensive overview of the role of oxadiazoles in the fight against tuberculosis, paving the way for future investigations and the development of effective therapeutic strategies.