Ethnopharmacological relevance: Thapsia garganica L. roots are used in Algerian traditional medicine for a number of ailments. It is used in a poultice as an antitussive treatment of acute bronchitis and pneumonia, in preparations with milk or oil taken orally to treat common lung diseases, and with the direct application of root sections for the soothing of dental pains. Aim of the study: The objective of this study was to evaluate the combined effect of microwave assisted extraction and gamma irradiation on sesquiterpene lactones in T. garganica extracts Materials and methods: To evaluate the combined effect of microwave assisted extraction and gamma irradiation on the highly bioactive compounds found in extracts of Algerian T. garganica, samples from different locations in Algeria were prepared by extraction from dried leaf and root samples of dried plant material, using different extraction methods Quantification of the compounds of interest was done using an HPLC. The antioxidant activity extracts was determined using the two free radical scavenging assays: the 2,2-diphenyl-picryl-hydrazyl (DPPH) and the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS). Results: It was found that location and extraction method had significant impact on the phytochemical composition of extracts. Gamma irradiation was found to have no effect on the phytochemical composition of the plant extracts or on their antioxidant properties. Conclusion: The study has shown that microwave assisted extraction is an effective method for investigating chemical compounds in T. garganica and the results support the notion that gamma irradiation for sterilisation do not alter the chemical composition. The authors wish to clarify that we cannot recommend the usage of any parts of T. garganica, in any form, for any remedy due to its very high toxicity.