This study's primary goal is to perform molecular docking analysis and screen for drug-likeness, medicinal properties, and toxicity properties of identified active compounds obtained from Citrullus lanatus leaves using gas chromatography-mass spectrometry. Molecular docking and gas chromatography-mass spectrometry were applied to the extracts. The leaf extracts of Citrullus lanatus were found to contain five compounds according to the gas chromatography-mass spectrometry analysis. While 5-isobutyl-2-methyl-N~3~-(1-naphthyl)-3-furamide compound from Vadodara city showed the best effectiveness in antidiabetic action, the results of the in silico molecular docking studies demonstrated that all five compounds have antidiabetic potential. All five compounds exhibit promising drug-likeness properties, medicinal chemistry, and toxicity. Citrullus lanatus leaves may therefore be a useful pharmaceutical agent in the management and treatment of complications associated with many therapeutic applications including diabetes.