AbstractBackgroundRecent studies have implicated oxidative stress, chronic neuroinflammation, functional cholinergic deficits, and glutamatergic pathway disruptions in the pathophysiology of dementia. However, certain medicinal plants are being used in the management of dementias by the inhabitants of Ibarapa Area of South‐Western Nigeria, hence this study.MethodEthno‐pharmacological survey of medicinal plants used in the management of dementias in Ibarapa Area of Oyo State, South‐Western Nigeria was conducted using semi‐structured questionnaires and open‐ended interviews. Phytochemical, antioxidant, anti‐inflammatory, anti‐nociceptive, and cholinesterase‐inhibiting screenings were conducted on selected medicinal plants (SMPs) using standard assays. Preliminary cytotoxicity screening of promising crude extracts were determined using brine shrimp lethality assay (BSLA). LD50, acute and sub‐chronic administrations of the SMPs into groups of mice were determined using Organization of Economic Cooperation and Development (OECD) 423 guideline. Haematological, biochemical, and histopathological examinations following single and repeated doses of crude extracts of SMPs into groups of mice were determined using standard assays. Behavioural studies using relevant mouse models were conducted. Mechanistic studies using cell lines are being carried out on the promising SMPs. Data are expressed as mean ± standard error of mean (SEM) and analyzed using one‐way analysis of variance (ANOVA) followed by post‐hoc test (Student‐Newman‐Keuls test).ResultThe ethnomedicinal survey revealed about 105 medicinal plants belonging to more than 50 families being used as memory enhancers in the management of dementias by the inhabitants of Ibarapa Area of Oyo State in south‐Western Nigeria. Phoenix dactylifera, Combretum mucranthum, Parquitena nigrescens, Crinum jagus, Blighia sapida, Entandrophragma utile, Ficus exasperate showed significant antioxidant, anti‐inflammatory, and anti‐cholinergic activities. Results of BSLA revealed LC50 values of 100 ‐ 1000 ppm for the screened plants. The oral LD50 values of crude methanol extracts of SMPs are 2000 ‐ 5000 mg/kg. Findings from haematological, biochemical, histological and behavioural assays following both single and repeated administrations of the tested SMPs in mice showed that they are safe and possess promising neurobehavioural potentials that warranted further exploration.ConclusionThe SMPs are safe, highly rich in beneficial phytochemicals, exhibited significant antioxidant, anti‐inflammatory, anti‐cholinesterase, nootropic and neuroprotective potentials thereby suggesting the rationale for their ethnomedicinal use in the management of NNDs.