Re-investigation of the MeOH extract of the seeds of Cucumis melo L. var. reticulatus (Cucurbitaceae) led to the isolation of a new chromone derivative (5,7-dihydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyl]chromone (5) and a triglyceride (1,3-di-(6Z,9Z)-docosa-6,9-dienoyl-2-(6Z) hexacos-6-enoylglycerol (1), together with three known compounds; -spinasterol (2), stigmasta-7,22,25-trien-3-ol (3), and D:B-friedoolean-5-ene-3--ol (4), are reported from this species for the first time. Their structures were determined by extensive 1D (1H, 13C, and DEPT) and 2D (1H-1H COSY, HMQC, and HMBC) NMR and mass spectral measurements. Compound 5 displayed significant cytotoxic activity against L5178Y cells, with an ED50 of 5 µM. The MeOH extract and 5 showed antioxidant activity using the DPPH assay.