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Initially, Isatin was treated with 4-amino acetanilide to form Isatin Schiff base, by the reaction of the free amino group on4-amino acetanilide with carbonyl group of Isatin in the presence of ethanol and glacial acetic acid with the elimination of water molecule. The obtained Isatin Schiff base was then treated with substituted aromatic aldehydes in the presence of potassium hydroxide and ethanol to form various Chalcone derivatives (C1-C7). The structures of the synthesized compounds (C1-C7) were examined and confirmed using IR, Mass spectroscopy, 1H-NMR and elemental analysis. By agar disc diffusion method, all given compounds were evaluated for their anti-bacterial activity against four bacteria at concentrations 25, 50 and 100 μg/ml. C4 and C6, were discovered to have possessed the most potent anti-bacterial activity.