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Oxidative stress induced by free radicals is the main cause of many human diseases. Plant‐derived antioxidant supplements can counter oxidative damage in cells. The purposes of this study were to investigate the effects of water extracts from dried seeds of Benincasa hispida (B. hispida) on antioxidant activity and how this related to total contents of phenolics and flavonoids in vitro. The levels of phenolic and flavonoid compounds were 81.3 ± 1.4 µg gallic acid /g and 486.8 ± 4.1 µg catechin/g dry mass, respectively. B. hispida showed DPPH (2,2‐diphenyl‐picrylhydrazyl hydrate), ABTS (1, 2,2′‐azinobis‐[3‐ethylbenzothiazoline‐6‐sulfonic acid]) and hydroxyl radical scavenging activity in a dose‐dependent manner, with maximum inhibition of 79.8 ± 0.2%, 82.3 ± 1.9% and 95.5 ± 0.8%, respectively. Inhibition of linoleic acid oxidation and nitrite scavenging activity were maximum 73.2 ± 1.0% and 73.6 ± 1.3% at 6 days and 1‐h incubation time, respectively. Our data suggest that the dried seeds from B. hispida could be used as a source of natural antioxidants in the food industry. PRACTICAL APPLICATIONS Other evidence suggests that the consumption of wax gourd promotes health. This is because of several important bioactive compounds such as lipids, protein, carbohydrates, fiber, minerals and vitamins that have already been isolated from wax gourd. Wax gourd is effective against diabetes, dropsy, diseases related to liver, leucorrhea and fever. It can strengthen the function of bladder and small and large intestines. It is also good for the detoxication of minerals. The findings of this study can demonstrate the antioxidant activity of the water extracts from B. hispida dried seeds. The nitrite and free radical scavenging effects of the extract would be useful to improve human health.