Purpose: High energy dietary patterns rich in fat and fructose can lead to neurological dysfunction that is not directly improved by oral functional compounds. This study found that the edible flavor eugenol may act directly on the hippocampus via the transnasal route to the brain to improve neurological dysfunction. Method: Fifty 6-week-old male C57/BL6N mice were divided into five groups: the control group received basal chow, and the model group was fed a high-fat(45% calorie购买SAGs), high-fructose(15% water) diet for 18 weeks and given eugenolBiomass allocation by intranasal drip(10 mg/kg) and different doses by gavage(10 mg/kg, 20 mg/kg). Neurological function was assessed by behavioral and pathological measures; the distribution and retention of eugenol in the brain was analyzed by metabolomics; the molecular mechanism of eugenol action in the hippocampus was analyzed by transcriptomics. Result: Both the oral and intranasal eugenol groups significantly reduced body weight, blood lipids, and blood glucose in mice compared to the control group. The intranasal drop of eugenol significantly improved the performance of mice on a high energy diet in the water maze and novel object recognition experiments. Timemetabolomics results showed that eugenol accumulated in the hippocampus and hypothalamus of mice within 12 hours of intranasal administration, whereas oral administration did not. The combined transcriptomic and metabolomic analyses showed that eugenol was significantly different from the moStaurosporine半抑制浓度del group in signaling pathways such as hippocampal neurotransmitter transmission, TRP signaling and apoptosis after transnasal drip. Subsequent cytological validation results showed that eugenol affected neuronal cell Ca2+ influx via TRPV1 signaling after brain entry, which in turn ameliorated neuronal apoptosis caused by high glucose environment via PI3K-Akt signaling. Conclusion: Eugenol improves neurological function at lower doses by the intranasal route compared to the transoral route.