Neuroglobin (Ngb) is an oxygen-binding globin protein that has been demonstrated to be neuroprotective against stroke and related neurological disorders. However, the underlying mechanisms of Ngb's neuroprotection remain largely undefined. Mitochondria play critical roles in multiple physiological pathways including cell respiration, energy production, free radical generation, and cellular homeostasis and apoptosis. Mitochondrial dysfunction is widely involved in the pathogenesis of stroke and neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's diseases. Accumulating evidence showed that elevated Ngb level is associated with preserved mitochondrial function, suggesting that Ngb may play neuroprotective roles through mitochondria-mediated pathways. In this paper we briefly discuss the mitochondria-related mechanisms in Ngb's neuroprotection, especially those involved in ATP production, ROS generation and scavenging, and mitochondria-mediated cell death signaling pathways.