There is a pressing need for better pharmacological treatment strategies for psychiatric disorders as current treatment often results in partial symptom remission and unwanted side effects. A point of entry may be the glutamatergic system since glutamatergic dysregulation contributes to multiple psychiatric disorders. We evaluated the evidence from randomized controlled trials (RCTs) regarding the use of the glutamatergic drug riluzole in mental illnesses; and conducted preliminary meta-analyses of its effectiveness in treating obsessive-compulsive disorder (OCD) and depression. A systematic search was performed using PubMed (Medline), Embase, Cochrane Database of Systematic Reviews and PsycINFO. Meta-analyses were performed using Comprehensive Meta-Analysis software. Twenty-three RCTs were included for qualitative analysis and showed positive effects of adjunctive/monotherapy riluzole in patients with OCD, depression, autism, substance abuse and schizophrenia. Seven studies were also used for quantitative analysis, which revealed positive but non-significant effects on OCD and depression. Riluzole was generally well tolerated with few serious adverse events. The studies included in this systematic review were highly heterogeneous and the number of studies was limited per diagnostic condition. Moreover, few studies have examined riluzole as a single treatment. We suggest carrying out further work to provide definitive evidence for the benefit of riluzole in psychiatric illness.