Gypsification is a common problem in weathered calcareous relics. In previous studies, the solutions of barium hydroxide in water and methanol were used as protectants for gypsification calcareous relics and showed significant differences in permeability. In this study, the underlying reasons for permeability differences between these two solutions were investigated using optical microscopy, ultraviolet–visible spectrophotometry, X-ray diffractometry, Fourier transform infrared spectroscopy, the phenolphthalein test and physical property characterizations. The results indicated that the permeability differences were primarily caused by the solutions’ reactivity. Specifically, owing to the high reactivity of barium hydroxide in water, it reacted rapidly with atmospheric CO2 and gypsum (the weathering product) to generate barium carbonate, barium sulfate and calcium hydroxide precipitates. These precipitates hindered the penetration of solution into weathered relics. In contrast, barium hydroxide in methanol did not react with atmospheric CO2 or weathered relics, which also kept the solution in a liquid state during the infiltration process. Therefore, the solution of barium hydroxide in methanol exhibited high permeability. Based on the above findings, this study is meaningful for applying barium protectants in the conservation of gypsification calcareous relics.