Abstract: The choice of therapy in mild to moderate level of psoriasis includes topical therapy. In silico is an analog computerized experiment which is similar to in vivo and in vitro biological experiment. Cyperus rotundus or nut grass has antipsoriatic activity so that it can be used as a topical herbal medicine in reducing psoriasis severity. The aim of this study was intended to evaluate the content of Cyperus rotundus using in silico analysis in psoriasis treatment. Active compound of extracted Cyperus rotundus is taken from the knapsack database. Simplified Molecular Input Line Entry System (SMILE) format is taken from the pubchem database. The predictions on skin barrier repair, immunosuppressors, anti-inflammatory and antipruritic agents are performed by using a pass server. The molecular mechanism of active compounds in the human body is taken from the search tool for interacting chemicals (STITCH) which is experimentally predicted; then it is computationally analyzed. Further pathway analysis uses cytoscape software. There are 21 active compounds on Cyperus rotundus. The potential of Cyperus rotundus as immunosuppressor, anti-inflammatory, and antipruritic is predicted to have activity that is examined computationally, but this has not been proven in laboratory experiment or has small potential. The highest potential of Cyperus rotundus bioactivity in improving skin barrier which has the most function is beta-selinene with an average value of probable to be active (Pa) 0.715 predicted to have high potential computationally and laboratory tests. Overall, Cyperus rotundus is a good option for psoriasis therapy in improving skin barrier function, immunosuppressors, antiinflammatory and antipruritic because it has beneficial effectiveness in terms of the availability and safety.