The primary objective of this study is to identify and analyze the lipid and flavonoid components present in Salvia fruticosa Mill, as well as to assess its potential antibacterial activity. Introduction: Salvia fruticosa Mill (SF) is considered a significant medicinal plant that is found all over the world. Method: The essential lipid contents (fatty acids and unsaponifiable matter), the volatile oil from leaves, and the antibacterial activity of various extracts were all evaluated. The lipid components were extracted with n-hexane then fractionated. Four flavonoids, namely luteolin, cosmos, cynaroside, andorientin, were isolated from the alcoholic extract of the plant by chromatographic and spectroscopic methods. The extracts were tested for their antimicrobial activity against various microorganisms by measuring the inhibition zone diameter using disc diffusion method. A molecular docking study was performed to assess the binding affinity of the flavonoids to the DNA gyrase enzyme, which is a crucial target for antibacterial drugs. Caryophyllene (18.70%), lab-13-ene,8,15-diol (15.93%), methyl linoleate (10.53%), and 1,8-cineole (8.24%) are the most prevalent components in the volatile oil, according to the GC/MS analysis. The lipid components were fractionated into three groups: the unsaponifiable fraction, the fatty acid OMe (FAME), and the insoluble fraction of the acetone (fatty alcohols and hydrocarbons). The obtained results show remarkable antifungal activity with chloroform extract against A. flavus and moderate activity against A. niger. Besides, the butanol and ethyl acetate extracts presented high activity against Sarcina sp. with inhibition zone of 22 mm. The microorganism B. cerus was affected moderately by ethyl acetate and chloroform extracts with inhibition zone of 14 and 12 mm, respectively. The methanol extract was active against C. albicans only. The fatty acids fraction inhibited the growth of A. flavus with inhibition zones of 8, 10 and 14 mm for different concentrations, respectively. The Docking results revealed that all compounds exhibited a promising interaction into the DNA-gyrase, which agrees with an experimental data got from the antibacterial activity assay. These results were obtained first for this plant, especially the results of molecular docking study in relation to antibacterial activity.