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Curcumin is a natural polyphenolic compound widely known to have antioxidant, anti‐inflammatory, and antiapoptotic properties. In the present study, we explored the neuroprotective effect of curcumin against lipopolysaccharide‐ (LPS‐) induced reactive oxygen species‐ (ROS‐) mediated neuroinflammation, neurodegeneration, and memory deficits in the adult rat hippocampus via regulation of the JNK/NF‐κB/Akt signaling pathway. Adult rats were treated intraperitoneally with LPS at a dose of 250 μg/kg for 7 days and curcumin at a dose of 300 mg/kg for 14 days. After 14 days, the rats were sacrificed, and western blotting and ROS and lipid peroxidation assays were performed. For immunohistochemistry and confocal microscopy, the rats were perfused transcardially with 4% paraformaldehyde. In order to verify the JNK‐dependent neuroprotective effect of curcumin and to confirm the in vivo results, HT‐22 …