Curcumin, a dietary polyphenol and major constituent of Curcuma longa (Zingiberaceae), is extensively used as a spice in Asian countries. For ages, turmeric has been used in traditional medicine systems to treat various diseases, which was possible because of its anti-inflammatory, antioxidant, anticancerous, antiepileptic, antidepressant, immunomodulatory, neuroprotective, antiapoptotic, and antiproliferative effects. Curcumin has potent antioxidant, anti-inflammatory, antiapoptotic, neurotrophic activities, which support its plausible neuroprotective effects in neurodegenerative disease. However, there is limited information available regarding the clinical efficacy of curcumin in neurodegenerative cases. The low oral bioavailability of curcumin may be speculated as a plausible factor that limits its effects in humans. Therefore, utilization of several approaches for the enhancement of bioavailability may improve clinical outcomes. Furthermore, the use of nanotechnology and a targeted drug delivery system may improve the bioavailability of curcumin. The present review is designed to summarize the molecular mechanisms pertaining to the neuroprotective effects of curcumin and its nanoformulations.