Background and Aim: Alzheimer’s disease (AD) poses a significant health-care challenge, often linked to cognitive decline caused by oxidative stress. This study investigated the potential neuroprotective effects of the Paederia foetida leaf extract (PFE) in rats that exhibited scopolamine-induced dementia mimicking AD. Materials and Methods: Forty-two male rats were treated with either donepezil (0.5 mg/kg) or PFE at doses of 250, 500, and 1000 mg/kg for 14 days before and 14 days after the beginning of Alzheimer’s-like symptoms after 14 consecutive days of scopolamine administration. Behavioral tests, including the open-field test for locomotor activity and the Morris water maze task for learning and memory assessment, were conducted. Neuronal cell counts and biochemical assays were performed to further analyze outcomes. Results: All groups exhibited normal locomotor activity. The scopolamine group displayed longer escape latency times, reduced time in the target quadrant, decreased number of surviving neurons, and increased malondialdehyde and decreased glutathione levels compared with the control group. However, pre-treatment with 1000 mg/kg PFE notably mitigated the neurotoxic effects of scopolamine. Conclusion: The neuroprotective properties of PFE are highlighted, suggesting its potential as a promising treatment strategy for AD. Keywords: Alzheimer’s disease, neuroprotection, oxidative stress, Paederia foetida, scopolamine.