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<br>Display Omitted<br>• Response surface methodology was applied to optimize supercritical fluid extraction conditions of alantolactone and isoalantolactone. • The optimized extraction conditions were pressure 20 MPa, extraction temperature 50 °C, carbon dioxide flow rate of 17 × 10−5 kg/s and extraction time of 40 min. • Freezing purification greatly improve the content of the target compounds by 30.7 wt.%.<br><b>Inula racemose</b> Hook.f. (<b>I</b>. <b>racemosa</b>) is a traditional herbal medicine with strong anti-fungal and anti-inflammation activity while alantolactone (AL) and isoalantolactone (IAL) are the major active compounds of this plant. The aim of this paper was obtaining AL and IAL from the radix of <b>I</b>. <b>racemosa</b> by supercritical fluid extraction (SFE) which was optimized by response surface methodology (RSM). Our results showed that, the optimal conditions for maximum extraction efficiency were as follows: pressure 20 MPa, extraction temperature 50 °C, carbon dioxide (CO2) flow rate of 17.0 × 10−5 kg/s and extraction time of 40 min. Subsequently, an efficient freezing method was developed for purification of AL and IAL in the crude extract obtained from SFE. After purification by freezing, the total content of the target compounds was greatly improved by 30.7%. The results demonstrate that SFE coupled with freezing would be a powerful technique for extraction and purification of AL and IAL from the radix of <b>I</b>. <b>racemosa</b>.