The cucurbitacins and glucosionalates (GLSs) and their hydrolyzed compounds protect plants from stresses. Foods containing GLSs have unique bitter taste and pungent odor. The bitterness in domesticated cucurbits (except for bottle gourd) is lost through domestication. Two genes, Bl ( bitter leaves ) and Bt ( bitter fruit ) control bitterness in Cucurbitaceae. KASP markers have been effectively deployed to differentiate bitter-free segregants in cucumber-breeding programs. Genes regulating bitterness in bottle gourd are not orthologs to the known bitterness genes in cucumber. Maintaining desired levels of seed glucosinolates (GLSs) without disrupting GLSs in vegetative tissues is a significant breeding challenge. However, by editing glucosinolate transporter ( GT ) genes by CRISPR/Cas9 system, it is feasible to lower the seed GLSs at globally acceptable levels without disrupting the synthesis in vegetative tissues to protect plants from pest damage. Divergent mass selection is also effective in modifying total and individual GLS contents.