Abstract: The well-documented problems regarding the harmful side effects and the continuous increase in the number of microorganisms that are resistant to the chemical antibiotics highlights the need for new strategies and new classes of antibiotics with low toxicity and high selectivity in their action. In the present study, aqueous and organic solvent extracts of the leaves, flowers and latex of Calotropis procera (Ait.) were tested for their antimicrobial activity. For this purpose, the disc diffusion bioassay and the Minimal Inhibitory Concentrations (MICs) of the tested botanicals were adopted. Results revealed considerable antimicrobial activities of the tested extracts. In all cases, the extraction solvent was a determinant factor for the extraction of antimicrobial agents. The leaf and latex methanolic extracts showed the strongest activities, where Escherichia coli, Staphylococcus epidermides, and Bacillus spp. were the most sensitive. In these cases inhibition zones ranged between 11.0 to 23.5 mm and minimal inhibitory concentrations between 0.25-1.5 mg mL-1. All extracts showed biocidal activities against all of the tested fungal strains with diameters of inhibition zones ranged between 9.0 and 26.5 mm. The latex methanolic was the most effective extract (inhibition zones ranged from 21.0 to 26.5 mm against Candida albicans, C. tropicalis, Penicillium chrysogenum and Saccharomyces cerevisiae). To test any synergistic effect between the latex methanolic and Ciprofloxacin and Clotrimazole, the extract was added to the tested antibiotics at concentrations equal 1/2, 1/4, 1/8 and 1/32 and 0 of the original MIC values. Results revealed that the MIC's of the two antimicrobial standards, were lowered indicating a synergistic interaction between the botanical and the conventional drugs. Present findings confer the utility of extracts and latex of C. procera in developing a novel antimicrobial biorationals of plant origin.