Obsessive-compulsive disorder (OCD) is a relatively prevalent mental disorder that poses significant health burdens on the community. Although current conventional medications have good efficacy for many patients, they can elicit a range of associated adverse effects. Plant-based compounds have been evaluated for different mental disorders, with a range of anxiolytic properties revealed. To determine the current evidence in the area, we conducted a systematic review using the electronic databases including PubMed, Scopus, and the Cochrane Library up to June 12, 2019, for pharmacological and clinical evidence of herbal medicines and phytochemicals with antiobsessive-compulsive effects. Additional search criteria were employed for locating research on the underpinning mechanisms of action. Results revealed that tentative low-quality evidence exists for several plant medicines, including Crocus sativus, Silybum marianum, Echium amoenum, Hypericum perforatum, and Withania somnifera, along with several natural molecules, including crocin, cannabidiol, and curcumin. Although more research is needed to confirm effectiveness, present preclinical studies indicate that monoamine pathway modulation (in particular serotonin reuptake inhibition) may be the most important anti-OCD mechanism among the studied natural compounds.