<p>Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and synaptic dysfunction. Growing evidence indicates that mitochondrial impairment is not merely a secondary consequence of pathology but an early and central driver of AD progression. Mitochondrial defects—including impaired glucose metabolism, reduced activity of key bioenergetic enzymes, disrupted calcium homeostasis, and abnormal fission–fusion dynamics—emerge before the formation of amyloid-β (Aβ) plaques and tau tangles, positioning mitochondrial dysfunction as a potential upstream trigger of neurodegeneration. These alterations amplify oxidative stress, promote mtDNA damage, and establish a self-perpetuating cycle that accelerates neuronal vulnerability. This review synthesizes recent mechanistic insights demonstrating how metabolic dysregulation, mtDNA mutations, and deficiencies in mitochondrial quality-control pathways converge to influence AD pathogenesis. Importantly, we highlight emerging therapeutic strategies aimed at restoring mitochondrial resilience—including antioxidants, metabolic modulators, mitophagy-enhancing agents, dietary interventions, and lifestyle-based approaches such as caloric restriction and physical activity. By integrating current molecular and translational findings, this work underscores mitochondria as a promising disease-modifying target and outlines therapeutic avenues with potential to slow or prevent AD progression (Graphical abstract).</p> Graphical Abstract <p></p>