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This review delves into novel TZD derivatives, encompassing their synthesis, structure\u2010activity relationships, and pharmacokinetic profiles. Various therapeutic potentials of TZDs are explored, including anticancer, antimicrobial, anti\u2010inflammatory, antioxidant, anticonvulsant, antihyperlipidemic, anticorrosive, and antitubercular activities. Additionally, it addresses mitigating side effects associated with marketed TZD derivatives such as weight gain, oedema, fractures, and congestive heart failure in type 2 diabetes mellitus management. The review elaborates on <jats:italic>in\u2005vivo, in\u2005vitro<\/jats:italic>, and <jats:italic>ex vivo<\/jats:italic> studies supporting different biological activities, alongside predicting ADME and drug\u2010likeness properties of TZDs. Computational studies are also integrated to elucidate binding modes and affinities of novel TZD derivatives. 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