Artemisia arborescens essential oil (EO), collected from two Palestinian regions, Bethlehem and Jenin, were extracted by hydro-distillation and examined for their chemical compositions, cytotoxic, antimicrobial, cyclooxygenase (COX) enzyme inhibitory effects, and their influence on neuronal (AMPA) receptors. The EO sample from Bethlehem A. arborescens had just 13 molecules, which accounted 100% of the total EO. Meanwhile, 18 molecules that accounted for 100% of the total EO were determined in the Jenin A. arborescens sample. β-thujone (89.64%), camphor (5.34%), and β-pinene (2.01%) were the major molecules in the Bethlehem EO sample, while β-thujone (79.16%), camphor (6.58%), and sabinene (3.44%) were the dominating components in the Jenin EO sample. Moreover, both EOs have antimicrobial effects against all of the examined microorganisms. The EO from Jenin has slightly higher cytotoxic potential against cervical adenocarcinoma (HeLa) cancer cells than the EO from Bethlehem, which has IC50 of 0.326 and 0.467 mg/mL, respectively. The COX inhibitory IC50 calculations showed that A. arborescens EO from Jenin has high potency against COX-1 (1.8 µg/mL). At the same time, the EO from Bethlehem was slightly more potent against COX-2 (IC50 =81.7 µg/mL). Both EOs show significant impacts on the different AMPAR types, yet Jenin EO shows more significant inhibition on amplitude, desensitization, and deactivation mechanisms generated by the receptors. Both EOs may be effective in reducing overexcitation of AMPARs and reducing the effects of ischemia. These results support the possible therapeutic application of A. arborescens EO from both regions to prevent and treat certain pathogenic infections, cancers, inflammations, and neurodegenerative diseases.