Technological advances show progressive neuronal loss, cognition, and motor function in neurodegenerative diseases that include Alzheimer?s, Parkinson?s, and Huntington?s which contribute to the most disabling conditions people live with. The current therapies aim only at the manifesting signs of a disease and not the root causes, and this after over thirty years of research. To meet this therapeutic need, innovative therapies that address the involved complex pathology of these diseases are required. Another promising approach in the search for new agents for the treatment of neurodegenerative diseases: Alkaloids of plant origin, which the nature has no lack as a chemist. In natural nitrogenous compounds called alkaloids, one detects a spectrum of pharmacological actions that suits the neuroprotective needs best. Huperzine A ? derived from Lycopodium species, is a neurological drug that is an acetylcholinesterase, while galantamine derived from Amaryllidaceae plants has revolutionized the treatment of Alzheimer disease by modifying the cholinergic system. Berberine, a naturally occurring alkaloid from the plant Berberis species and reserpine, an alkaloid from Rauwolfia species, have been shown to have a potential therapeutic use in the management of PD since BER and RES possess antioxidant, anti-inflammatory and anti-dopaminergic properties in an experimental model of PD. Recent studies suggest that it is possible to learn how alkaloids can help with the protection and prevention of neurodegenerative diseases due to their ability to stop protein clustering. These are just a few of the challenges that need to be addressed in order to make these compounds with miraculous activity of natural origin real in the clinic, including issues of scalability, bioavailability, and pharmacokinetics. Advancements in the synthetic biology, nanotechnology and artificial intelligence can potentially alter the therapeutic applicability of the alkaloids. In this review, a discussion of the clinical applications and implication of alkaloids extracted from plants for medicinal purposes, as well as the actions mechanism and potential future applications is covered. Alkaloids, which blends indigenous wisdom with modern scientific research, has unearthed solutions that if realized, hold the prospects towards ending neurodegeneration.