Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degenera- tion of motor neurons. Mitochondrial dysfunction may be an important intersection of various pathological changes in ALS. It is mainly manifested by impaired oxidative phosphorylation, increased reactive oxygen species (ROS), disordered calcium homeostasis, abnor- mal mitochondrial dynamics and autophagy, axonal transport disorders and mitochondrial pathway apoptosis. ALS-associated genes and pathological proteins may disrupt mitochondrial homeostasis through various mechanisms. Current mitochondria-targeted therapeutic strategies mainly include mitochondria-targeted antioxidant therapy, modulation of mitochondrial fission and fusion, enhancement of mi- tophagy and mitochondrial quality control as well as metabolic modulation. However, the results are not entirely consistent across differ- ent models. This review summarizes the main mechanisms and treatment progress of ALS-related mitochondrial dysfunction. Its clinical translation limitations is also discussed.