Chalcones are natural biocides. Several publications appear every year covering the synthesis of chalcones because they exhibit an array of pharmacological activities. In this study, some condensation reactions of 1-Indanone with substituted benzaldehydes were carried out under different reaction conditions. The chalcone products were converted to their corresponding 2,4-Dinitrophenylhydrazone derivatives and evaluated against five gram-positive and eight gram-negative bacteria for their in vitro antibacterial property. Antimicrobial activity was observed against many of the tested strains, with zones of inhibition ranging from 10 to 28 mm. In many cases, the hydrazone derivatives were more active than their chalcone precursors. The best results were obtained against gram-negative bacteria for most of the compounds. Compound 1b was the most active with its minimum inhibitory concentrations (MICs) against six strains of bacteria ranging from 15.6 to 31.3 µg/ml, hence, could be developed as an antibacterial agent against infections caused by some gramnegative bacteria such as Pseudomonas aeruginosa and Salmonella typhimurium.