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The biodiversity of medicinal plants have many economic importances and improve human health. Many biologically active compounds were isolated from plants that were traditionally used in folkloric medicine . These compounds can be either a new drug or a base for new drug. The antibacterial activity of the traditionally used Cymbopogon schoenanthus and Senna holosericea, collected from Alabwa region, Saudi Arabia was determined using agar well diffusion method. The plants were collected, identified and extracted using both different organic solvents (methanol, ethanol and acetone) and hot water. The tested bacteria were multidrug resistant, Escherichia coli, Micrococcus lutes, Klebsiella pneumonia, and Shigella sonnei. Maximum activity was recorded for the methanolic extract Senna holosericea against all tested bacteria with inhibition zone diameter ranged from 31-35 mm and MIC value of 37.5 μm/ml. Lower activities was recorded for the methanolic extract of Cymbopogon schoenanthus against all tested bacteria with MIC ranged from 37.5 -70 μm/ml. Weak antimicrobial activity or no activities were recorded for hot water extracts of the two tested plants. No toxicity was recorded for the methanolic extracts of the two tested plants using Artemia salina as test organism. In conclusion, the two tested plants, used traditionally in medicine by popular, recorded antimicrobial activities against the multidrug resistant bacteria with no toxicity.