•Brain allometry across higher macroevolutionary hierarchies in snakes seems conserved.•In lizards the macroevolutionary brain allometry at higher hierarchies is variable.•Brain size in Crotalinae pit-vipers evolved without anatomical energetic trade-offs.•Body design could drive conservation of macroevolutionary brain allometry in snakes. Despite historical interest in brain size evolution in vertebrates, few studies have assessed variation in brain size in squamate reptiles such as snakes and lizards. Here, we analyzed the pattern of brain allometry at macroevolutionary scale in snakes and lizards, using body mass and snout vent length as measures of body size. We also assessed potential energetic trade-offs associated with relative brain size changes in Crotalinae vipers. Body mass showed a conserved pattern of brain allometry across taxa of snakes, but not in lizards. Body length favored changes of brain allometry in both snakes and lizards, but less variability was observed in snakes. Moreover, we did not find evidence for trade-offs between brain size and the size of other organs in Crotalinae. Thus, despite the contribution of body elongation to changes in relative brain size in squamate reptiles, snakes present low variation in brain allometry across taxa. Although the mechanisms driving this conserved pattern are unknown, we hypothesize that the snake body plan plays an important role in balancing the energetic demands of brain and body size increase at macroevolutionary scales. We encourage future research on the evolution of brain and body size in snakes to test this hypothesis.