The transcription factor Nrf2 (nuclear factor-erythroid 2 p45-related factor 2) play a crucial role in cellular redox and metabolic system. Activation of Nrf2 may be an effective therapeutic approach for neuroinflammatory disorders, through activation of antioxidant defences system, lower the inflammation, line up the mitochondrial function, and balancing of protein homeostasis. Various recent studies revealed that many of active substance obtained from plants have been found to activate the Nrf2 and to exert neuroprotective effects in various experimental models, raising the possibility that activation of Nrf2 may be an effective therapeutic approaches for neuroinflammatory disorders. The objective of this review was to evaluate the neuroprotective property of natural substance against neuroinflammatory disorders by reviewing the studies done till today. The outcomes of various in vitro and in vivo examinations have shown that natural compounds producing neuroprotective effects in neuronal system via activation of Nrf2. Herein, we also reviewed the studies to understand the role of Nrf2 for curing CNS disorders. Here we can conclude, herbal/natural moieties having potency to fight and prevent from neuroinflammatory disorders due to their abilities to activate Nrf2 pathway.