Medicinal plants represent the main source of therapeutic agents. The WHO stated that most of the world population use herbal drugs because they belief that, they are safe, cheap and affordable. Many modern drugs show resistance to pathogenic bacteria as one of the forms of antimicrobial resistance which is considered from the top problematic issues in the world. Fortunately, medicinal plants can be the hero for fighting this problem by providing new antibacterial agents. Sudan is a virgin area for phytomedicine research due to its diversity of traditions besides the diversity of climates that leads to variety of plant species. Acacia polyacantha tree is widely available in Sudan and is used traditionally for treating many bacterial diseases. This study aimed to analyze the hydro-ethanol extract of Acacia polyacanthaleaves using GC-MS analysis and to determine its antibiogram against two standard bacterial strains by well diffusion method, besides molecular docking and ADMET studies.A. Polyacantha leaves was extracted by cold maceration using Ethanol 70%. GC-MS analysis was carried out for the first time and proved to contain 23 compounds. The major compounds were4-O-Methylmannose (60.28%), Phytol (8.2%) and Adenosine N6-phenylaceticacid (4.74%). The extract was tested for antibacterial activity against standard bacterial strains of Gram +ve bacteria (Staphylococcus aureus) and Gram -ve bacteria (Pseudomonas aeroginosa) by well diffusion method which was active against S.aureus and inactive against P.aeruginosa. Moreover, binding mode and pharmacokinetics properties of the compounds present in the extract were further studied and reported. In conclusion, A. Polyacantha leaves extract is rich in phytochemical compounds having antibacterial activity.