The aerial parts ofMentha longifolia L. are used as herbal remedies for curing different diseases through traditional Bedouin medicine. The antioxidant activity of the ethanolic extracts of M longifolia was investigated measuring peroxyl radical-scavenging activity by ORAC assay, with Trolox (a water-soluble analogue of α-tocopherol) employed as reference compound. In addition, the total content of phenolic compounds estimated by the Folin-Ciocalteau method and the identification of the polyphenols using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) have been performed. Furthermore, the effect of these extracts on cell viability and intracellular ROS production was assayed using the U373-MG human astrocytoma cell line in a H2O2-induced oxidative stress model. Results showed that the major type of polyphenols found were benzoic acids, cinnamic acids, flavones and flavanones. The total phenolic content was 37.7 mg gallic acid/g sample and the ORAC value was 1.355 .mol TE/mg sample. The data obtained in cellular assays demonstrated that these ethanolic extracts protected H2O2-induced astrocyte damage by increasing cell viability and inhibiting production of intracellular ROS. These results suggest that the investigated extracts obtained from the aerial parts of M longifolia have antioxidant potential related to their phenol content which have important beneficial health effects, especially in those disease associated with ROS.