Background: Imipenem-cilastatin is one of the commonly used antibacterial drugs for the treatment of severe infections in clinical practice. Since its launch, apart from seizures, other neuropsychiatric adverse events(AEs) have been rarely reported. This study comprehensively evaluates the neuropsychiatric AEs of imipenem-cilastatin in the real world through the FDA Adverse Event Reporting System (FAERS) database. Methods: This study searched the FAERS database for neuropsychiatric AEs related to imipenem-cilastatin from the first quarter of 2004 to the fourth quarter of 2024. We evaluated the association between imipenem-cilastatin and neuropsychiatric AEs through various disproportionality analysis methods. Results: We obtained a total of 1822 patients and 2899 reports of neuropsychiatric AEs related to imipenem-cilastatin from the data. The common AEs included epilepsy, seizure, delirium, dysphoria, and mental disorder. Additionally, we identified some unexpected signals such as uraemic encephalopathy, persecutory delusion, logorrhoea, and staring. The median age of patients with overall neuropsychiatric AEs with imipenem-cilastatin was 70 years, and the median time to onset of overall neuropsychiatric AEs with imipenem-cilastatin was 2 days, with median onset times of 2 days for seizures and 3 days for delirium-related AEs,no statistical differences in median onset times were found in gender and age subgroups. Conclusion: This study provides real-world insights into the use of imipenem-cilastatin, which is an important supplement to clinical application. Elderly patients should be closely monitored for neuropsychiatric AEs during early use of imipenem-cilastatin