Medicinal plants have a great role in influencing health all over the world. There are few studies for the phytochemical investigations in medicinal plants were conducted in Saudi Arabia especially in Albaha region in south-western Saudi Arabia. Therefore this study focused on the detection of the phytochemical composition of the most dominant eighteen natural medicinal plant varieties found in Albaha region. Aqueous extracts of the dried aerial parts of these plants were prepared. The phytochemical composition of these extracts was investigated. Also, the antioxidants and anti-cancer activity of these plants' extracts were evaluated. The results revealed that phenols, flavonoids saponins and glycosides cyanides were the most abundant phytochemical components in the investigated plants. Dodonaea viscosa, Solanum incanum, Olea europaea subsp. cuspidata and Aerva javanica were the highest plants in their phytochemical components and their antioxidant capacity. Their antioxidant capacity recorded 38, 32, 22 and 14% increase more than that of the standard (Ascorbic acid) respectively. Also, these plants showed an interesting anticancer effect compared to the other studied plants. Their IC50 against studied cancer cell lines was lower than 20 μg/ml. This low IC50 is an evidence to be a promising anticancer agent for crude extracts. Thus the present study highlighted the importance of these detected plant varieties as a source of anticancer agents. More intensive studies are needed to verify the most effective chemical components in these investigated plants.