Objective To investigate the protective effect and underlying mechanism of liraglutide on brain injury in lipopolysaccharide （LPS）-induced septic mice. Methods Ninety C57BL/6 mice were randomly divided into three groups （n = 30）： the Control group， the Sepsis group （LPS）， and the LPS + Liraglutide group （LPS + Lira）. The LPS and LPS + Lira groups received intraperitoneal injections of LPS （15 mg/kg）， while the Control group received an equal volume of normal saline. The LPS + Lira group was subcutaneously injected with liraglutide （200 µg/kg） twice daily for 3 consecutive days， starting 2 days before the LPS injection. Results Significant differences were observed among the three groups in terms of survival rate， brain water content， the number of normal pyramidal cells in the hippocampal CA1 region， apoptosis rate， oxidative stress markers， inflammatory cytokine levels， and related protein expression （P < 0.05）. Further pairwise comparisons showed that， compared to the Control group， the LPS group had a significantly reduced survival rate （P < 0.05）， increased brain water content （P < 0.05）， decreased number of normal pyramidal cells in the hippocampal CA1 region （P < 0.05）， and an elevated apoptosis rate （P < 0.05）. Additionally， oxidative stress and inflammatory cytokine levels were significantly higher （P < 0.05）， with increased expression of NLRP3， Casp1 p10， Caspase-3， and Bax proteins （P < 0.05）， and decreased expression of Bcl-2 （P < 0.05）. The LPS + Lira group showed significant improvement in all these indicators compared to the LPS group （P < 0.05）. Conclusion Liraglutide exerts a protective effect against LPS-induced septic brain injury by inhibiting the activation of the NLRP3/Caspase-1 signaling pathway， thereby reducing inflammation， oxidative stress， and apoptosis.