Mitochondria are key players in the energetic metabolism, providing energy for almost every cellular process, playing also a central role in the maintenance of normal cellular function. The brain has a high energy demand; hence neurons are especially susceptible to disturbances in oxygen and nutrient availability. Such disturbances, as observed in pathologies such as ischemia/reperfusion or stroke, can represent an insult with irreversible consequences to cell viability. Mitochondrial dysfunction resulting from pathological events represents a serious threat to cellular viability. Since mitochondria are tightly related with a variety of cellular processes, the loss of mitochondrial function frequently represents a point of no return towards cell death. In this aspect, mitochondria can also play an important role in the decision of cellular fate - apoptosis versus necrosis. The search for compounds aiming at neuroprotection through the preservation of mitochondrial function might prove to be a suitable therapeutic approach for the treatment of neurodegenerative diseases. Examples of such molecules are phenolic compounds, which can be found in natural sources such as in plant extracts. Phenolics present in Hypericum perforatum are endowed with strong antioxidant and neuroprotective properties. In fact, the observed protection is suggested to be, at least in part, mediated through mitochondria-based effects, indicating a potential application for the use of such compounds or extracts in neuroprotection.