Abstract The aim of this work is to investigate the compounds from selected plants (Coleus forskohliiand and Commiphora gileadensis) grown in Aseer region presumed to be active. Phytochemical screening was carried out for the two plants resulting in a high amount of terpenoids and flavonoids. Various bioassays (antimicrobial and anticancer) for their fractions were performed and the results revealed the activities of the plants fractions. IC50 value of petroleum ether fraction of C.forskohlii was (2.8, 2.58 and 1.73μg/ml) against Human Breast ""MCF-7"", Human Colon ""HCT-116"" and Human Liver ""HEPG-2"" respectively and IC50 value of n-butanol fraction of C.gileadensis against cancer cell lines was (4.48, 5.38 and 0.12 μg/ml). Antimicrobial activity showed that ethyl acetate for both plants are highly active. The essential oils constituents were studied by steam distillation and estimated for the both plants by (gas chromatography - mass spectrometry), where Thymol compound is the major constituents of C. forskohlii and α-Calacorene is the major compound in C. gileadensis. The chromatographic purification by successive columns using silica gel and Sephadex LH-20 leads to isolation of 13 compounds. Structure determination by nuclear magnetic resonance (NMR) spectroscopic (1D and 2D-NMR) and mass spectrometric revealed the presence of Syringic acid (B), Luteolin (C),Euphol (E), 3,4,5-trihydroxy benzoate (D) and 4-O-[β-Dglucopyrasonyl]-2-isopropyl-5-methyl phenol (G) which is new compound, isolated from Coleus forskohlii. From Commiphora gileadensis, Eudesmic acid (I) and flavonoid glycoside; 3-O-[β-Dglucopurasonyl]-luteolin (M) have been isolated. It is important to note that there is 2-Methylbutyl benzoate (A) compound from C.forskohlii that was assumed from NMR analysis. So, there are five compounds were isolated for the first time from both plants. The Bioassay of available pure compounds indicates that compounds B, F, I and K respectively have anticancer effect against (Human Breast ""MCF-7"", Human Colon ""HCT-116"" and Human Liver ""HEPG-2""). Antimicrobial activity of compound A is in the range (13-30 mm) proofing an excellent inhibition activity compared to N