The present work focuses on evaluation of the chemical composition and antioxidant activity of the hydro-methanolic extract of Melissa officinalis from Algeria. The liquid chromatography-mass spectrometry analysis allowed the identification of six compounds: caffeic acid, caftaric acid, hydroxyjasmonic acid glucoside, caftaric acid glucoside, rosmarinic acid and sagerinic acid. The in-vitro antioxidant activity of the hydro-methanolic extract was evaluated by using four different methods including: radical scavenging assay (DPPH), scavenging activity (ABTS), cupric reducing antioxidant capacity (CUPRAC), and ferric reducing power assay. The extract exhibited a relatively strong antioxidant activity compared to the synthetic antioxidants. The highest radical scavenging activity was registered using DPPH and ABTS methods, IC50= 20.53±2.64 μg/mL and 22.50±0.67 μg/mL, respectively. These results suggest that Melissa officinalis L. could be considered a potential source of natural antioxidants with potential interest in the agrochemical and pharmaceutical industries.