Salvia officinalisL. (Lamiaceae) is a Mediterranean species, naturalized in many countries. In Jordan, it is used in traditional medicine as antiseptic, antiscabies, antisyphilitic, and anti-inflammatory, being frequently used against skin diseases. This study aimed the assessment of the antifungal and anti-inflammatory potential of its essential oils, and their cytotoxicity on macrophages and keratinocytes. The oils were investigated by gas chromatography and gas chromatography-mass spectrometry and the antifungal activity was evaluated against yeasts, dermatophyte andAspergillusstrains. Assessment of cell viability was made by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and thein vitroanti-inflammatory potential was evaluated by measuring nitric oxide production using lipopolysaccharide-stimulated mouse macrophages. The main compounds ofS. officinalisoils were 1,8-cineole (39.5–50.3%) and camphor (8.8–25.0%). The oils revealed antifungal activity against dermatophyte strains and significantly inhibited NO production stimulated by LPS in macrophages, without affecting cell viability, in concentrations up to 0.64 μL/mL. This is the first report addressing thein vitroanti-inflammatory potential ofS. officinalisoil. These findings demonstrated that bioactive concentrations ofS. officinalisoils do not affect mammalian macrophages and keratinocytes viability making them suitable to be incorporated in skin care formulations for cosmetic and pharmaceutical purposes.