This study was aimed to analyze the chemical composition and biological activities of extracts of Salvia fruticosa and S. lanigera originated from Libya. Dichloromethane, ethyl acetate, methanol, ethanol and water extracts obtained from wild growing plants were analyzed for the composition using HPLC-DAD, which revealed presence of phenolic acids and flavonoids, mainly in alcoholic and water extracts. Total phenolic and flavonoid contents, as well as anti-oxidant activity using 2.2-diphenyl-1-picrylhydrazyl (DPPH), 2.2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid diammonium salt (ABTS), ferric reducing anti-oxidant potential (FRAP) and β-carotene bleaching (β-CB) assays were determined spectrophotometrically. Extracts of S. fruticosa exhibited stronger activity in all applied assays, especially ethanol extract in DPPH assay (IC50, 29.55 μg/mL) and in β-CB assay (85.11%). The ethanol and water extracts were selected for further investigation, because of their wide usage in phytotherapy. The extracts were screened for the antimicrobial activity against 11 bacteria (six Gram-negative and five Gram-positive) and seven fungi using microdillution method. Ethanol extracts showed stronger activity than water extracts, particularly against Gram-positive bacteria. Trichophyton mentagrophytes was the most sensitive to the water extract of S. lanigera (MIC, minimal inhibitory concentration and MFC, minimal fungicidal concentration, 8 mg/mL). Cytotoxic activity on human carcinoma cell line HCT-116 was determined by 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyl tetrazolium bromide (MTT) cell viability assay, where only ethanol extract of S. fruticosa demonstrated certain activity (IC50, 375.96 μg/mL). The testing of anti-neurodegenerative activities of extracts showed better tyrosinase inhibiting effect (55.26–74.66%) than standard kojic acid (33.93–51.81%), while the extracts were less effective against acetylcholinesterase compared with standard galanthamine. According to the obtained results, S. fruticosa and S. lanigera originated from Libya have proved to be the promising source of natural compounds possessing a range of biological activities.