Mitochondria are essential for β-cell function, coupling glucose metabolism to ATP production and insulin secretion. In diabetes, β-cell mitochondrial dysfunction arises from oxidative stress, impaired quality control and disrupted dynamics, leading to reduced oxidative phosphorylation, defective insulin release and progressive cell loss. Key transcriptional regulators link genetic susceptibility to mitochondrial dysfunction in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). These disruptions impair mitophagy, mitochondrial translation and redox homeostasis. Therapeutic strategies that restore mitochondrial function, including mitophagy enhancers, mitochondrial antioxidants, and transcriptional regulators, have shown potential in preserving β-cell integrity. As mitochondrial failure precedes β-cell loss, targeting mitochondrial pathways may represent a critical approach to modifying diabetes progression.