Scutellaria baicalensis (S. baicalensis) root extract has been used for a long time in Oriental medicine and the cosmetics industry due to its natural anti-oxidant properties in disease treatment. However, comprehensive studies comparing the physiological activities of different S. baicalensis root extracts are lacking. Specifically, there is a need to compare S. baicalensis root hydrothermal extract (SBHE), S. baicalensis root 75% ethyl alcohol extract (SBAE), and S. baicalensis root supercritical fluid extracts (SBSEs) simultaneously. In this study, we extracted S. baicalensis roots using three different methods: hydrothermal, 75% ethyl alcohol, and supercritical fluid extraction. We then evaluated their radical scavenging activities, SOD-like activity, anti-bacterial activities, and the production of inflammatory factors. Among the extracts tested, the S. baicalensis root supercritical fluid 35°C extract (SBSE35) exhibited superior overall physiological activities. Notably, only the SBSEs demonstrated anti-bacterial activity against Staphylococcus aureus, whereas SBHE and SBAE did not. SBHE and SBAE increased interleukin (IL)-6 levels (p ≤ 0.05). Additionally, SBHE and SBAE showed a slight decrease in IL-8 at low concentrations, but an increase in IL-8 production in a concentration-dependent manner. In contrast, SBSE35 significantly reduced both IL-6 and IL-8 levels (p ≤ 0.05). These findings suggest that SBSE35 has greater potential for improving human health in the cosmetics and pharmaceutical fields.