Sri Lanka is listed as the top 34th biodiversity hotspot globally and has the highest biodiversity per unit area of terrestrial in the Asian continent. Intriguingly, it has been reported that 3771 flowering plant species are grown in Sri Lanka, of which 927 (24%) are endemic to the country, and 1430 species are considered medicinal plants. Surprisingly, it is reported that up to 40% of all new molecular entities submitted to the Food and Drug Administration (FDA) approval are either natural products or natural product-derived compounds. This chapter aims to explore the therapeutic potential of Sri Lankan plants/natural products in neuroprotection as possible synergistic targets of the nuclear factor erythroid (NF-E2)-related factor 2 (Nrf2) pathway. Nonetheless, the symptoms of neurological diseases are different; oxidative stress plays a central role in pathogenesis, thus, Nrf2 activation will counteract common pathogenic processes involved in neurodegener-ative/neuromuscular disorders. Therefore, targeting Nrf2 signaling may provide a therapeutic option to delay onset, slow progression, and ameliorate symptoms of neurological disorders. However, when translating from the bench to the bedside, the knowledge of the timing of Nrf2 modulating compounds and dosage is crucial to define at which point should an Nrf2 activator be used versus an Nrf2 inhibitor. In this scenario, blends of natural products that synergize and provide multi-site action on Nrf2 regulation via different pathways are vital and will pave the way for the development of evidencebased effective neuro-nutraceuticals with a stride of innovation.