Diabetes mellitus, a prevalent metabolic disorder, necessitates continuous exploration for innovative therapeutic agents. Indolinedione has garnered attention for its potential as an antidiabetic scaffold for its structurally diverse nucleus. The search for novel and effective antidiabetic agents has led to the exploration of natural compounds and synthetic derivatives. The review commences with an in‐depth exploration of the biochemical underpinnings of diabetes mellitus, emphasizing rational design strategies employed for modifying the indolinedione nucleus, encompassing various synthetic methodologies aimed at enhancing its pharmacological properties and docking studies. The multifaceted pharmacological properties and diverse synthetic derivatives of indolinedione offer a fertile ground for further exploration in preclinical and clinical studies. As research in this field progresses, indolinedione may emerge as a valuable addition to the arsenal of antidiabetic therapeutics, providing new avenues for the effective management of diabetes mellitus.