Neurodegenerative diseases (NDDs), including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ASL), are a diverse set of diseases characterized by gradual deterioration and specic loss of neurons that are physiologically or anatomically connected. This loss severely impairs cognitive behavioral function [89–91]. NDDs are characterized by the buildup of improperly folded proteins in the central nervous system (CNS), that form insoluble aggregation or inclusions. This leads to the gradual degeneration of neurons in the affected areas [92]. The rates of morbidity and mortality of these illnesses are experiencing a signicant increase due to the aging of the worldwide population [93]. NDDs are projected to sur­pass cancer as the second most prevalent death cause worldwide by 2024, as stated by the World Health Organization. Due to the limited regenerating capacity of the human neural system, the disease’s course is irreversible [89]. Nanotechnology is an emerging method for delivering drugs that can potentially overcome obstacles in the CNS such as the blood- brain barrier (BBB) [94]. The therapeutic benets of drug release rely on their ability to effectively avoid the immune system, tra­verse BBB, and specically accumulate in the tissues of interest, any form of obstruction during the administration of drugs reduces the effectiveness of medicinal treatments. Over the past few years, numerous nanodelivery technologies have been created for diverse applications in the pharmaceuti­cal sector [95]. Interest in using polyphenolic compounds is growing for medical purposes to prevent and treat many degenerative and long- term illnesses, such as neurological disorders, cardiovascular problems, and cancer [94]. The extract of Ginkgo biloba leaves has a signicant concentration of polyphenolic components such as myricetin, quercetin and kaempferol [96]. The article states that extract has neuroprotective benets in the recombinant mouse model (G93A) of amyotrophic lat­eral sclerosis (ALS). The administration of the extract orally signicantly reduced the aberration in motor function and increased the duration of survival [97]. Moreover, research ndings demon­strated a signicant reduction in the degeneration of motor neuron cells in the spinal cord within the ALS mice model when treated with the Gingko biloba plant extract. Additionally, there are several polyphenolic substances that show benecial benets in ALS, including ginseng [98], genistein [99], epigallocatechin gallate [100], and resveratrol [101]. Currently, there are numerous unsolved issues about the effective transportation of drugs into the CNS. The specic difculties can be attributed to various reasons, such as the existence of the BBB, the blood- spinal cord barrier, and the inherent characteristics of the medications themselves, such as insufcient biostability, low solubil­ity, and undesired effects among others [102]. Due to low bioavailability, the traditional medication cannot effectively reach the area of interest in individuals who have ALS to promote a full recovery, However, the nanotechnological methods employ specially designed nanocarriers that show great promise in delivering individual or combined drugs that can eliminate biological obstacles, enable real- time monitoring while minimizing widespread adverse consequences, enhance interaction with specic sites, and enhance drug stability and availability [103].