AbstractPiper cubeba L.f. fruit, specifically its seeds, has been used traditionally to strengthen memory. This study aimed to examine the neuroprotective effect of a nanoemulsion of P. cubeba essential oil ( NPCEO ) in a scopolamine-induced rat model of Alzheimer’s disease. Male Wistar rats were divided into six groups: negative control, normal control, citicoline 200 mg/kg, NPCEO 100 mg/kg, NPCEO 200 mg/kg, and NPCEO 400 mg/kg. The brain was used for biochemical measurements, including tumor necrosis factor ( TNF )-α, interleukin ( IL )-1β, IL -10, acetylcholinesterase ( AChE ) activity, brain-derived neurotrophic factor ( BDNF ), nuclear factor erythroid 2-related factor 2 ( Nrf2 ), lipid peroxidase activity, and catalase ( CAT ) levels. Cognitive performance was examined using water-E maze ( WEM ), novel object recognition test ( NORT ), and open field test ( OFT ) methods. The results showed that NPCEO could reduce neuroinflammation and improve cognitive function impairment caused by scopolamine. In conclusion, P. cubeba could improve cognitive function in scopolamine-treated rats, possibly through its antioxidant and anti-inflammatory properties in the hippocampus and cerebral cortex.