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Background Several findings suggest neuroinflammation as a contributing factor for the onset of psychiatric disorders such as Alzheimer’s disease, depression, and anxiety. There is increasing evidence pointing out that the Mediterranean diet influences brain and behavior. Mediterranean herbs and spices have been shown to be within those components of the Mediterranean diet involved in cognitive enhancement. Thus, we investigated the influence of Mediterranean natural extracts (MNE), Rosemary extract (RE) and Glycyrrhiza glabra root extract (GGRE), on cognitive behavior. Results Adult zebrafish were exposed to RE or GGRE (100 and 250 mg/L) treatments. Both MNE improved memory retention during the T-maze test, although no improvements were observed during the novel object preference. Similarly, chronic administration of RE (150 mg/Kg) and GGRE (150 mg/Kg) improved, respectively, spatial and retention memory, as assessed by the Morris Water Maze (MWM), and the Elevated Plus Maze (EPM) in healthy male rats. However, no improvements were observed during the novel object recognition. Finally, male, and female rats were chronically treated with lipopolysaccharide [(LPS) 300 ug/kg] and orally administered with RE. Interestingly, RE reversed LPS-induced cognitive deficit during the MWM and EPM in female rats. Conclusions We found that MNE improved cognition in both zebrafish and rats. Moreover, MNE rescued LPS-induced cognitive impairment in a gender-specific manner. Therefore, our study supports the view that zebrafish represent a valuable preclinical model for drug discovery in neuroscience. These findings contribute to an exciting and growing body of research suggesting that MNE may play an important role in the prevention of cognitive impairment.