Mitochondria are the primary source of energy production in neurons, supporting the high energy consumption of the nervous system. Inefficient and dysfunctional mitochondria in the central nervous system have been implicated in neurodegenerative diseases. Therefore, targeting mitochondria offers a new therapeutic opportunity for neurodegenerative diseases. Many recent studies have proposed that plant-derived natural products, as pleiotropic, safe, and readily obtainable sources of new drugs, potentially treat neurodegenerative diseases by targeting mitochondria. In this review, we summarize recent advances in targeting mitochondria in neurotherapeutics by employing plant-derived natural products. We discuss the mechanism of plant-derived natural products according to their mechanism of action on mitochondria in terms of regulating biogenesis, fusion, fission, bioenergetics, oxidative stress, calcium homeostasis, membrane potential, and mitochondrial DNA stability, as well as repairing damaged mitochondria. In addition, we discuss the potential perspectives and challenges in developing plant-derived natural products to target mitochondria, highlighting the clinical value of phytochemicals as feasible candidates for future neurotherapeutics.