TRADITIONAL medicinal plants are an important economic source of raw materials for the drug industry. Nowadays, searching for new sources of drug raw materials is an important issue to meet the ever increasing demands. Therefore, quantitative and qualitative phytochemical screening of the dominated xerophytes inhabiting Wadi Sudr, South Sinai, including Retama raetam, Reaumaria hirtella, Tamarix nilotica and Zygophyllum dumosum, was performed. The accumulation levels of some natural bioactive products including phenols, flavonoids and saponins were determined during spring and summer. The investigated species exhibited significant increases in total free amino acids during spring, while they tend to accumulate total soluble sugars, sucrose and secondary metabolites including phenols, tannins and saponins during the dry summer season. Such increments in these metabolites were concomitant with the greatly reducing power capacity. Moreover, the antimicrobial activities of extracts from these shrubs were evaluated against four pathogenic microorganisms (2 bacterial species; Escherichia coli and Staphylococcus aureus and 2 fungal species; Candida albicans and Aspergillus fumigatus). Of the tested alternatives, methanolic extract was the most active fraction, while Tamarix nilotica was the most active plant species against the four tested microorganisms, especially Candida albicans. Furthermore, The MIC of the methanolic fraction of Tamarix nilotica and its effect on ergosterol and leakage of intracellular components of cells of Candida albicans showed that this shrub displays its fungicidal effects by targeting the ergosterol biosynthesis in Candida albicans and disrupting the membrane integrity. In conclusion, these shrubs are promising new sources for potent antioxidants and useful antimicrobial agents.