AbstractCadmium (Cd) is a prevalent industrial and environmental contaminant that accumulates in the tissues of animals and humans. In particular, one of the regions most affected by Cd-induced neurodegeneration is the hippocampus. Linalool (Lin) is a monoterpene capable of traversing the blood–brain barrier owing to its low molecular weight and high lipophilicity. This study sought to establish the possible neuroprotective effects of Lin against Cd-induced hippocampal neurodegeneration by focusing on the 4-hydroxynonenal (4-HNE)/Nuclear factor kappa B (NF-κB) signaling pathway. The 28 male rats used in the experiment were randomly (n = 7) distributed into four groups. The control group was not administered. The Cd group received CdCl2 at a dose of 3 mg/kg (cumulative 21 mg/kg) for the first 7 days of the experiment. The Cd + Lin group was given 3 mg/kg CdCl2 for the first 7 days of the experiment and 100 mg/kg Lin for 14 days throughout the experiment. The Lin group was administered Lin at a dosage of 100 mg/kg/day. After all treatments were finished, the rats’ brain tissues were taken out on the 15th day of the experiment. In this study, Cd increased oxidative stress parameters and decreased antioxidant enzyme levels in hippocampus tissue. In addition, Cd caused an increase in NF-κB and pro-apoptotic Caspas3 levels, which play an important role in inflammation in the hippocampus. Lin treatment against Cd exposure showed a therapeutic effect by suppressing oxidative stress, inflammation, and apoptosis. Lin may exert a neuroprotective effect by regulating the 4-HNE/NF-κB signaling pathway in Cd exposure-induced hippocampal neurodegeneration.Graphical Abstract