Genetic diversity among 17 Jordanian snake melon (Cucumis melo var. flexuosus) landraces was investigated using 8 AFLP primer combinations and 14 ISSR molecular markers. The eight AFLP primer combinations produced 403 bands among which 219 (54%) were polymorphic with the polymorphic information content (PIC) ranged from 92.1% to 95.5%. The Unweighted Pair Group Method with Arithmetic Average (UPGMA) classified the landraces into two groups based on Dice similarity coefficient, ranging from a high of 0.88 to a low of 0.22% similarity. Bootstrapping of the obtained AFLP-clusters ranged from 33 to 97. The 14 ISSR primers produced 63 bands, among which 27 (43%) were polymorphic, and classified the landraces into two groups ranging from a high of 0.97 to a low of 0.39% similarity. Bootstrapping of the obtained ISSR clusters ranged from 2 to 96. Both AFLP and ISSR markers were successful in amplifying informative bands for different snake melon landraces and showed moderate level of positive correlation (r = 0.71) based on Mantel test. While the principal component analysis explained 34% of the total variation, AFLP and ISSR markers were successful in characterizing and identifying potential important population sources for snake melon breeders.