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Green Chemistry or environmentally benign chemistry is the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances. Hydrazone, a derivative of aldehyde and ketones plays a key role in medicinal chemistry and is reported for various biological activities such as antibacterial, anti-inflammatory, analgesic, anticancer, antifungal, and antioxidant. There are various synthesis methods for hydrazone derivatives like stirring, reflux, and microwave irradiation. This study reported the microwave-assisted synthesis of hydrazone derivatives of isoindole with good yields in a few minutes. The prepared derivatives of isoindole were characterized by spectral techniques and also showed excellent antimicrobial activity against selected bacteria and fungi.