Old World camels exhibit many unique traits for adaptations to desert environments, distinct from New World camels within the same family. Here, we conducted a comparative genomic analysis of three Old World camel species relative to four New World camel species, as well as cattle, pigs, mice, and humans to search for genes showing positive selection and specific variations in Old World camels. We identified genes under positive selection, genes with specific small indels, and inactivated genes associated with the unique lipid metabolism and skin characteristics of Old World camels. Especially, through experimental validation, we confirmed the inactivation of , a gene encoding a prominent bitter taste receptor, which could enable Old World camels to consume certain toxic plants with a bitter taste to other mammals. These findings provide insights into the genetic basis underlying the distinctive energy metabolism, water-salt homeostasis, and dietary adaptations of Old World camels.