Nearly 40% of all new molecules submitted for Food and Drug Administration approval are either natural products or derivatives. Curcumin derived from the rhizome of Curcuma longa exhibits a wide pharmacological spectrum, encompassing antioxidant properties, suppression of neuroinflammatory cytokines, and regulation of cellular stress responses, and regulate autophagy and mammalian target of rapamycin (mTOR) signaling. Disruptions in mTOR signaling pathways are associated with neurodegenerative diseases. In response to oxidative stress, mTOR can modulate processes such as apoptosis and autophagy, often promoting tissue repair under. Additionally, the interaction between mTOR and other signaling cascades is reported to be crucial in human health. Notably, mTOR is linked with key pathways, including NF-κB, Akt, phosphatidylinositol 3-kinase (PI3K), AMPK, TFEB, and ERK1/2, which collectively influence inflammation, programmed cell death, cell survival, and oxidative stress. Curcumin has been reported to suppress the PI3K/Akt/mTOR signaling cascade and activate autophagy via AMPK, ULK1, and Beclin-1 pathways, promoting the degradation of misfolded proteins and damaged organelles. This chapter aims to explore the mechanistic role of curcumin in regulation of mTOR and autophagy pathways promoting neuroprotection.