Bacopa monnieri (L., BM) is a traditional Ayurvedic medicinal herb recognised for its efficacy in relieving acute pain and inflammation, as related to selective inhibition of cyclo-oxygenase-2 (COX-2) enzyme and consequent reduction in COX-2-mediated prostanoid mediators. BM is also associated with cognitive enhancing (nootropic) activity including improving memory free recall, observed after prolonged intake (>3 months). It is likely that the time frame required to exert an effect in the brain reflects regulation by BM of chronic inflammation and oxidative stress associated with aging and chronic diseases, and other polypharmacological effects. We report down-regulation by BM of NO and TNF-α in stimulated RAW 246.7 macrophages and of IFN-γ in stimulated human blood cells. Furthermore, in human blood cells, IL-10 was slightly elevated indicating polarisation towards a regulatory T cell phenotype. These results provide further supportive evidence to justify the clinical evaluation of BM for managing diseases involving chronic systemic and brain inflammation driven by the innate immune system.