Sideritis scardica Griseb., Lamiaceae (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of antimicrobial infections, gastrointestinal complaints, inflammation and rheumatic disorders. This study reports a comparison between conventional (hydrodistillation HD and solvent extraction SE) and alternative (supercritical carbon dioxide SC CO₂) extraction methods regarding the qualitative and quantitative composition of the obtained extracts as analyzed by GC and GC-MS techniques and their anitimicrobial activity. Different types of extracts were tested, the essential oil EO obtained by HD, EO-CO₂ and AO-CO₂ obtained by SC CO₂ at different preasures 10 and 30 MPa, at 40 °C, respectively, and the fractions A, B, C and D obtained by successive solvent extraction (SE) A: ethanol, B: diethyl ether, C: ethyl acetate and D: n-butanol). While EO was characterized by the presence of the high percentage of oxygenated monoterpenes and sesquiterpenes (30.01 and 25.54%, respectively), the rest of the investigated samples were the most abundant in fatty acids and their esters and diterpenes (from 16.72 to 71.07% for fatty acids and their esters, and from 23.30 to 72.76%, for diterpenes). Microbial susceptibility tests revealed the strong to moderate activity of all investigated extracts against the tested microorganisms (MIC from 40 to 2,560 μg/mL). Although differences in the chemical compositions determined by GC and GC-MS analysis were established, the displayed antimicrobial activity was similar for the all investigated extracts.