The present study investigated the composition of essential oil and evaluation antimicrobial and antioxidant of the ethanolic extract of the aerial parts of Helichrysum leucocephalum. Gas chromatography/mass spectrometry (GC/MS) revealed the presence of 43 compounds which represents 96.8% of the total oil. Carvacrol (20.36%), acetophenone (11.17%) and azulene (7.09%) were identified as the main principal components of the essential oil. H. leucocephalum ethanolic extract exhibited a high phenol content (114.13±0.89 mg gallic acid equivalent (GAE)/g of dry plant) while total flavonoid content was found to be 43.26±0.70 mg quercetin equivalent (QE)/g of dry plant). In order to evaluate antioxidant efficacy of the essential oil and ethanolic extract, DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging and ferric reducing antioxidant power. (FRAP) assays were conducted. The ethanolic extract demonstrated significant DPPH free radical Inhibitory activity (IC50 = 61.35±0.07 µg/mL) and ferric reducing ability (IC50= 113.43±0.58 µg/mL) while the essential oil declared a weak antioxidant properties. Antimicrobial screening revealed higher degree of inhibition for essential oil of the aerial parts of H. leucocephalum against Staphylococcus aureus and Escherichia coli both with MIC value, 16 µg/mL. Additionally the essential oil of H. leucocephalum exhibited antifungal properties when tested against Candida albicans (MIC50, 32 µg/mL).