This study comprehensively analysed the chemical composition of the cuticle in pitaya fruits. The total coverage amount of the waxes versus cutin monomers accumulated at a ratio of 0.6, corresponding to masses per unit of 30.3 μg·cm−2 and 50.8 μg·cm−2, respectively. The predominant wax mixtures were n-alkanes in homologous series of C20–C35, dominated by C31 and C33; as well as triterpenoids with an abundant amount of uvaol, lupenon, β-amyrinon, and β-amyrin. The most prominent cutin compounds were C16- and C18-type monomers, in which 9(10),16-diOH-hexadecanoic acid and 9,10-epoxy-ω-OH-octadecanoic acid predominated, respectively. The average chain length (ACL) of aliphates in pitaya fruit cuticle (30.5) was similar to that estimated in leaf waxes, and higher than that in most of the fruit and petal waxes that have been reported. We propose that the relatively high ACL and wax/cutin ratio might enhance the cuticular barrier properties in pitaya fruit cuticle to withstand drought.