Saffron or Crocus sativus L. (C. sativus) has been widely used as a medicinal plant to promote human health, especially in Asia. The main components of saffron are crocin, picrocrocin and safranal. The median lethal doses (LD50) of C. sativus are 200 mg/ml and 20.7 g/kg in vitro and in animal studies, respectively. Saffron has been suggested to be effective in the treatment of a wide range of disorders including coronary artery diseases, hypertension, stomach disorders, dysmenorrhea and learning and memory impairments. In addition, different studies have indicated that saffron has anti-inflammatory, anti-atherosclerotic, antigenotoxic and cytotoxic activities. Antitussive effects of stigmas and petals of C. sativus and its components, safranal and crocin have also been demonstrated. The anticonvulsant and anti-Alzheimer properties of saffron extract were shown in human and animal studies. The efﬁcacy of C. sativus in the treatment of mild to moderate depression was also reported in clinical trial. Administration of C. sativus and its constituents increased glutamate and dopamine levels in the brain in a dose-dependent manner. It also interacts with the opioid system to reduce withdrawal syndrome. Therefore, in the present article, the effects of C. sativus and its constituents on the nervous system and the possible underlying mechanisms are reviewed. Our literature review showed that C. sativus and its components can be considered as promising agents in the treatment of nervous system disorders.