Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes progressive loss of motor neuron. The mechanism of ALS involves the aggregation and accumulation of several mutant proteins, such as copper / zinc superoxide dismutase (SOD1). Previous reports have shown that excessive oxidative stress, associated with mitochondrial dysfunction and mutant protein accumulation, contributes to the progress of ALS. Having recently synthesized novel organic gem-dihydroperoxides (DHPs) with high anti-oxidant activity, we examined whether DHPs reduce the mutant SOD1-induced intracellular aggregates involved in oxidative stress. We found that, among DHPs, 12AC2O significantly inhibited mutant SOD1-induced cell death and reduced the intracellular mutant SOD1 aggregates. Moreover, immunofluorescence staining with redox-sensitive dyes showed that 12AC2O reduced the excessive level of intracellular mutant SOD1-induced reactive oxygen species (ROS). Additionally, ESR analysis showed that 12AC2O exerts a direct scavenging effect against the hydroxyl radical (-OH) and the superoxide anion (O₂-). Collectively, these results suggest that 12AC2O is a very useful agent in combination with other agents against ALS.