Alpha-mangostin is a xanthone with antioxidant properties isolated from mangosteen fruit. The reactive oxygen species (ROS) scavenging capacity and the potential protective effect of alpha-mangostin against the mitochondrial toxin 3-nitropropionic acid (3-NP) in primary cultures of cerebellar granule neurons (CGNs) were studied in the present work. It was found that alpha-mangostin was able to scavenge in a concentration-dependent way singlet oxygen, superoxide anion and peroxynitrite anion. In contrast, alpha-mangostin was unable to scavenge hydroxyl radicals and hydrogen peroxide. Furthermore, alpha-mangostin was able to ameliorate in a concentration-dependent way the neuronal death induced by 3-NP. This protective effect was associated with an amelioration of 3-NP-induced reactive oxygen species formation. It is concluded that alpha-mangostin is able to scavenge directly several ROS and has a neuroprotective effect against 3-NP in primary cultures of CGNs, which is associated with its ability to ameliorate 3-NP-induced ROS production.