Extraction of medicinal compounds from St John's Wort was performed using supercritical ethanol. The supercritical fluid extraction parameters were optimized via response surface methodology which included a central composite design. The independent variables were extraction temperature (ranging from 300°C to 340°C), extraction times (ranging from 60 to 120 min), and plant concentration (ranging from 8% to 12%). The response was the St John's Wort extract yield. The extraction temperature was the most significant factor which affects St John's Wort yields according to statistical results. The coefficient of determination was estimated to be 0.98 which indicates the effectiveness of the model and its adaptability to the experimental data. The extract of St John's Wort was comprised of a wide array of compounds including phenols, acids, acid esters, and alkanes. The most prominent components of the extract of St. John's Wort in terms of their relative concentrations were linoleic acid ethyl ester, oleic acid ethyl ester, hexadecanoic acid ethyl ester, and nonacosane.