As the use of plastic-containing materials in our daily lives becomes increasingly common, exposure to nanoplastics accordingly becomes inevitable. Micro and nanoplastics released from large amounts of plastic waste constitute a serious environmental problem. Therefore, this study aimed to examine the effects of polystyrene nanoplastic (PS-NP) on the hippocampus. Material and method: Thirty Wistar albino rats, 15 male and 15 female, aged 6–8 weeks, were used in the research. These were randomly divided into three groups of five males and five females each. A five-minute open field test was applied to all rats on the first and last days of the study. Three groups of rats (Control, NP1 and NP2) received the standard chow and water. Additionally, rats in the first neoplastic group (NP1) received 25 mg/kg PS-NP and rats in the second nanoplastic group (NP2) received 50 mg/kg PS-NP, at the same time each day by oral gavage. The rats were sacrificed under deep anesthesia at the end of four weeks. The hippocampi were removed and subjected to histopathological and biochemical analyses. Results: Green fluorescent dots were detected in the hippocampi of both dose groups receiving nanoplastics (NPs) administered orally to female and male rats. Histopathological examination revealed neuronal degeneration in the hippocampi of male and female rats from both dose groups. However, while no significant difference was observed among the groups in terms of changes in antioxidant enzyme values and open-field test data in male rats, significant differences in peroxidase (POD) and glutathione S-transferase (GST) values and fecal boli and grooming numbers were determined in female rats exposed to NPs. In conclusion, exposure to NP substances extend as far as the hippocampus, causing neuronal damage and behavioral problems.