Introduction: Salvia libanotica (sage) is one of most famous and traditional herbs popular throughout the Arab world. Extracts of S. libanotica are found to be useful as traditional medicine. The current study aimed to further explore the phyto-constituents of the plant and its biological activity. Methodology The present study investigated the phytochemical constituent of sage and its synergism with essential oils using classical method. Biological activity was evaluated as immunomodulatory activity, anti-bacterial, cytotoxic and anti-cancer activity in vitro. Results: One hundred gram of ethanolic crude extract was prepared from sage leaves using classical method; its combination with essential oil was prepared as 1:1 ratio. Phytochemical studies demonstrated positive results for tannins, flavonoids and triterpenes/sterols. Immunomodulatory activity revealed that ethanolic extract is effectively inhibiting the free radicals generated during inflammation. Mild antibacterial activity was found against all gram negative bacteria in ethanolic extract but not with essential oils. Whereas, gram positive bacteria Staphylococcus aureus and Bacillus subtilis were significantly (p<0.05) inhibited by ethanolic extract as well as synergistic combination of olive oil and balsam oil. Our results demonstrated that ethanolic extract with balsam oil possess significant activity (p<0.005) against Bacillus subtilis up to 80% inhibition. Furthermore. For anticancer potential on HeLa cells, combination of ethanolic extract with balsam oil was able to show mild activity 44% cell growth inhibition. However, ethanolic extract of sage was found to be toxic to fibroblast cells with IC50 value of 11.5+0.7. Conclusion. Results suggested that ethanolic extracts of most famous herb sage usually consume as tea is toxic to normal cells system as tested on fibroblast, conversely its synergistic effect with olive oil and balsam oil reduces the toxicity. Inhibition of free radical by ethanolic extract may be because of its toxic effect. Extract also showed limited anticancer activity against HeLa cells in presence of balsam oil. Hence, sage could be a leading plant against gram positive pathogen when combined with essential oils with reduced toxicity, however ethanolic extract of sage is potentially cytotoxic.