Barbula fallax Hedw., Erythrodontium julaceum (Schwaegr.) Par., and Bryum argenteum Hedw. are typical rock mosses growing on rocks in different terrestrial habitats. In this study, B. fallax and E. julaceum, which are epilithic mosses growing in rock desertification in Guizhou, China, were used as ecophysiological mosses in a combination of field investigations and laboratory experiments. We also investigated the reference moss B. argenteum, which is a widely distributed moss in habitats with soil as substrate. Our research focused on the response of the antioxidant defense system of epilithic mosses to drought stress. Most antioxidant defense indicators increased initially, then declined at later stages of drought stress. In contrast, the carotenoid content increased constantly. In addition, there was an initial increase (albeit variable) in relative membrane permeability, with this parameter showing a parabolic trend in all of the epilithic mosses. Among the three species, E. julaceum demonstrated the strongest resistance followed by B. fallax and then by B. argenteum. The epilithic mosses displayed stronger resistance compared to the native mosses; the increase in O_2~(-·) content and other reactive oxygen species (ROS) at the early stage of drought stress induced the enzymatic and non-enzymatic scavenging systems to sequester ROS. Moreover, the radical scavenging ability and strong drought tolerance was maintained. The longterm growth of bryophyte under drought conditions in a karst environment can help eliminate the intense response of mosses to drought stress as they adapt.