Datura is a well-known toxic plant, and several cases of death due to Datura intoxication have been reported. It has been documented as a plant with hallucinogenic properties. This study aimed to determine the biochemical and neurological effects of hydroethanolic seed extracts of Datura metel on the hippocampus and cerebellar cortex of adult rats. Twenty-five adult rats were assigned into five (5) groups (A, B, C, D, and E). Group A served as the negative control, and B served as the positive control, administered with lead acetate. While groups C, D and E were treated with 150mg/kg, 300mg/kg, and 600mg/kg body weight of the seed extracts. The animals were humanely sacrificed after 14 days of exposure. Haematoxylin, eosin stain, and immunohistochemical staining were carried out for neurofilament proteins (NFP) and neuro-specific enolase (NSE). Brain tissues for biochemical analysis were homogenized, and the level of superoxide dismutase (SOD), catalase, malondialdehyde, and glutathione S-Transferase were measured. Results showed a non-statistically significant increase in SOD, catalase, and GST. However, there was a statistically significant decrease in the level of MDA. Oral administration of hydroethanolic seed extracts of Datura metel in adult rats created changes in the histology of the hippocampus and cerebellar cortex of the rats, such as perineural vacuolation and apparent reduction in neuronal cells. The results of the immunohistochemical investigation point to a dose-dependent increase in NFP, while NSE was markedly expressed.