Phenolic composition of different extracts of honeydew melon seeds and their antioxidant activity was determined for the first time. Phenolic compounds were identified using a reversed phase high performance liquid chromatography with diode array detection (HPLC-DAD) method. Results showed the identification of five phenolic compounds in water extract namely gallic acid and its derivative, hydroxybenzoic acid and catechin derivatives and caffeic acid. There were nine phenolic compounds identified in methanol–water extract, which are caffeic acid, two vanillic acid derivatives, ellagitanins, quercetin-3-rutinoside, derivatives of syringic acid and ellagic acid. The amounts of gallic acid, caffeic acid and catechin were higher among all phenolic compounds. Total phenolic compounds and radical scavenging activity were higher in water and methanol–water extract than their corresponding methanol extracts. In conclusion, melon seeds are a good source of natural antioxidants with significant biological functions and may serve as food ingredients and as fortifying material for maintaining shelf life.