Neurodegenerative diseases have complex etiologies, however, neuroinflammation and oxidative stress are important markers in this pathogenesis and, in this sense, cannabinoids, especially CBD, have been identified as potential therapeutics for playing a neuroprotective role. Studies have demonstrated the neuroprotective effect of cannabinoids and derivatives of Cannabis sativa L in diseases of the central nervous system due to their interaction with the endocannabinoid system through receptors and other molecular targets. The aim of this review was to provide an overview of the endocannabinoid system and a summary of the clinical and preclinical findings of the therapeutic use of cannabinoids in epilepsy, multiple sclerosis and Parkinson’s disease, pointing out interactions with molecular targets and the potential for neuroprotection of CBD. Electronic searches were carried out in international databases, including studies that presented consistent data on this subject. Significant therapeutic effects of CBD were shown for epilepsy and Parkinson’s disease, while nabiximols contributed to the reduction of spasticity, being a frequent option for the treatment of multiple sclerosis. Although much has been projected on the therapeutic potential of cannabinoids for neurological disorders, there is a long way to go in the search for strong scientific evidence of their pharmacological effectiveness.