Mitochondrial diseases encompass a heterogeneous group of inherited disorders resulting from dysfunction of the mitochondrial respiratory chain, the primary site of cellular energy production. These diseases may arise from mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) encoding mitochondrial proteins, affecting tissues with high energy demands such as the brain, heart, and skeletal muscle. Clinically, mitochondrial diseases manifest with a wide spectrum of symptoms, including myopathy, encephalopathy, lactic acidosis, stroke-like episodes, and multisystem involvement. Pathophysiologically, impaired oxidative phosphorylation leads to reduced Adenosine triphosphate (ATP) synthesis and increased reactive oxygen species (ROS), contributing to cellular damage and metabolic derangements. Syndromes such as MELAS, MERRF, Leigh syndrome, and Kearns–Sayre syndrome illustrate the diversity of phenotypes and genotypes. Diagnosis involves biochemical assays, neuroimaging, muscle biopsy, and genetic testing, with emerging techniques enhancing the detection of heteroplasmic mutations and nuclear gene defects. Current management is largely supportive, focusing on symptom control and metabolic stabilization. Therapeutic strategies include mitochondrial cofactors (e.g., CoQ10, L-carnitine), antioxidants, and emerging gene therapy approaches. Advances in molecular diagnostics and personalized medicine hold promise for targeted interventions and improved prognostic outcomes.