Ethnopharmacological relevance: Cyperi Rhizoma (CR) derives from the rhizome or tuber of Cyperus rotundus L. of Cyperaceae. It is an herbal medicine which has been widely used in different healthcare systems like in China, India, Iran, and Japan. In Chinese medicine, CR could promote the flow of Qi in the Liver and Sanjiao channels, regulate menstruation and alleviate pain. Clinically, CR is used for depression, flatulence, hypochondriac pain, and dysmenorrhea. Thus, it has a long history and significant curative effect for the treatment of various Qi stagnation symptoms. Aim of this review: This review focuses on explaining the major antidepressant mechanisms of CR, and assessing the shortcomings of existing work. Besides, clinical applications, pharmacological effects and their corresponding chemical compositions and quality control of CR have been researched. Materials and methods: The search terms “Cyperus rotundus L.” was used to obtain the literatures from electronic databases such as Web of Science, ScienceDirect, PubMed, and China National Knowledge Infrastructure (CNKI). The information provided in this review to illustrate material basis of CR were only limited to papers which reported on the chemical compositions and pharmacological effects simultaneously. Result: The study showed that CR has significant application in Qi stagnation, like depressed liver, stomach, and bowel disorders, etc. in different countries or districts. Aqueous extract, EtOH extract, essential oil, total oligomeric flavonoids and five other extracts were effective constituents displaying pharmacological activities such as antibacterial, antioxidant, neuroprotective, antihemolytic, and anti-inflammatory effect. 41 kinds of specific components like α-cyperone, nootkatone exhibited corresponding pharmacological activities mentioned above. Different concentrations of ethanol extract, essential oil, decoction of CR and monomer composition like α-cyperone, rotunduside G had anti-depressant effects. Conclusions: In the present study, we have provided scientific information and research developments on traditional uses, phytochemical compositions and corresponding pharmacological activities, and quality control status on CR. The antidepression effect and its corresponding chemical compositions were generalized separately. The pharmacological activities studies should be more focused on the reflection of traditional clinical values. CR could be a significant potential herbal medicine to develop antidepressant drugs with lower side effects.