Chemical investigation of the methanolic extract of the seeds of Cucumis melo L. var. reticulatus (Cucurbitaceae) afforded three new chromone derivatives; 5,7-dihydroxy-2-[2-(4-hydroxyphenyl)ethyl]chromone 3, 5,7-dihydroxy-2-[2-(3,4-dihydroxyphenyl)ethyl]chromone 4, and 7-glucosyloxy-5-hydroxy-2-[2-(4-hydroxyphenyl)ethyl]chromone 6, together with three known compounds; β-amyrin 1, β-sitosterol 2, and β-sitosterol-3- O-β-glucopyranoside 5. Their structures were established by UV, IR, 1D and 2D NMR, in addition to mass spectroscopic data and comparison with literature data. The n-hexane and methanolic extracts were evaluated for their antimicrobial activity, as well as cytotoxic activity using the brine shrimp bioassay.