Background: The incidence of cognitive decline has been proposed to rise exponentially in the coming years. Therapies targeting molecular pathways involved in the enhancement of memory and energy regulation could be a major breakthrough in the prevention or management of dementia in susceptible populations.Objectives: This study investigated the effects of aqueous extracts of Cola nitida (AECONS) and Garcinia kola (AEGAK) on glutamate level and Na+ /K+ -ATPase activity in the hippocampus and hypothalamus of male Wistar rats. Methods: Adult male Wistar rats (170-200) were randomly allotted into groups (n=5/group); control (distilled water p.o.), AECONS1 (200 mg/kg), AECONS2 (400 mg/kg), AEGAK1 (200 mg/kg), AEGAK2 (400 mg/kg), AECONS1+AEGAK1 and AECONS2+AEGAK2. The extract was prepared and the administration was done daily for 6 weeks. Results and Discussion: Administration of AECONS or AEGAK increased plasma, hippocampal and hypothalamic glutamate, Na+ /K+ -ATPase activity, NO, SOD except hippocampal glutamate in AECONS1/AEGAK1, Na+ /K+ -ATPase activity and SOD in AEGAK1, hypothalamic glutamate and SOD in AECONS1 when compared with control. Besides, MDA level decreased in AEGAK2 and hippocampal but not hypothalamic MDA decreased in AEGAK1 compared with control. However, concomitant administration of AECONS and AEGAK enhanced plasma, hippocampal and hypothalamic biomarkers except hypothalamic MDA level. The present study demonstrates that AECONS and AEGAK synergistically enhance hippocampal and hypothalamic glutamate and Na+ /K+ - ATPase activity, which are accompanied by NO and SOD-dependent antioxidant enrichment. Conclusion: These findings, therefore, suggest that AECONS+AEGAK could be a better therapeutic candidate in hippocampal-hypothalamic-related neurodegenerative diseases.