Accumulating evidence indicates that amyloid β (Aβ) peptide can cause neurotoxicity in Alzheimer's disease (AD). SOMCL-668 is a novel selective and potent sigma-1 receptor allosteric modulator. In this study, we found that SOMCL-668 improved cognitive functions in Alzheimer’s disease animal model 3xTg mice. We revealed the protective effects of SOMCL-668 against Aβ- induced toxicity in PC12 cells as a model of Alzheimer’s cell damage. PC12 cells were pretreated with SOMCL-668 and then exposed to Aβ for 24h. Then the protective and anti-apoptotic effects of SOMCL-668 in PC12 cells were investigated. Our studies revealed that SOMCL-668 protected and rescued PC12 cells from Aβ- induced cell death. Further study showed that SOMCL-668 significantly ameliorated cell death due to Aβ insult by restoring abnormal changes in intracellular ROS, and mitochondrial membrane potential. Western blot analysis demonstrated that SOMCL-668 activated the extracellular regulated kinase ERK1/2 pathway. According to these findings, it seems that SOMCL-668 possesses anti-apoptotic effects and may be a valuable protective candidate against the progression of Alzheimer’s disease.