We aimed to assess the anti-inflammatory and antioxidative properties of KHG26792, a novel azetidine derivative, in amyloid β (Aβ)-treated primary microglial cells. KHG26792 attenuated the Aβ-induced production of inflammatory mediators such as IL-6, IL-1β, TNF-α, and nitric oxide. The levels of protein oxidation, lipid peroxidation, ROS, and NADHP oxidase enhanced by Aβ were also downregulated by KHG26792 treatment. The effects of KHG26792 against the Aβ-induced increases in inflammatory cytokine levels and oxidative stress were achieved by increasing the phosphorylation of Akt/ GSK-3β signaling and by decreasing the Aβ-induced translocation of NF-κB. Our results provide novel insights into the use of KHG26792 as a potential agent against Aβ toxicity, including its role in the reduction of inflammation and oxidative stress. Nevertheless, further investigations of cellular signaling are required to clarify the in vivo effects of KHG26792 against Aβ-induced toxicity. [BMB Reports 2017; 50(12): 634-639].