“The medicinal properties of cannabis and cannabinoid-derivative are entirely investigated and known. In addition, the identification of psychotropic plant cannabinoids has led to more studies regarding the cannabinoid system and its therapeutic features in the treatment and management of clinical symptoms of neuroinflammatory disorders, such as multiple sclerosis (MS), Parkinsons disease (PD), and Alzheimers disease (AD). In fact, cannabinoid agonists are able to control and regulate inflammatory responses. In contrast to the cannabinoid receptor type 1 (CB1) and its unwanted adverse effects, the cannabinoid receptor type 2 (CB2) and its ligands hold promise for new and effective therapeutic approaches. So far, some successes have been achieved in this field. This review will discuss an outline of the endocannabinoid system’s involvement in neuroinflammatory disorders. Moreover, the pharmacological efficacy of different natural and synthetic preparations of phytocannabinoids acting on cannabinoid receptors, particularly in MS, PD, and AD, will be updated. Also, the reasons for targeting CB2 for neurodegeneration will be explained.”