Mineral scaling and scaling-induced wetting are critical issues in membrane distillation (MD) during treatment of saline wastewaters. Gypsum scaling and scaling-induced wetting in MD were successfully regulated by heterogeneous crystallization with in-line granular filtration in this study. Stable water recovery increased from 32.5 % to more than 52.5 % in one-cycle operation, depending on filter media properties. Because a large mass of crystals were retained or/and adsorbed in the granular filter, the scaling mass on membrane surface was reduced by 41.2 %, 23.1 %, 54.7 % and 78.1 % by filter charged with activated carbon, sand, fiber and activated alumina, respectively. When activated carbon, sand, fiber and activated alumina were used, the final MD fluxes were 1.58, 1.04, 1.96 and 3.43 times that without filter, and permeate conductivity decreased by 43.0 %, 46.8 %, 83.2 % and 81.3 %, respectively. The multi-cycle tests showed that heterogeneous crystallization gradually occurred in the granular filter, thereby promoting seeding-induced crystallization that reduced gypsum scaling and scaling-induced wetting in MD. Excellent anti-scaling and anti-wetting performance of in-line granular filtration was also confirmed for synthetic and real industrial wastewater. The results of this study provide guidance for mineral scaling control in MD to allow resource utilization for saline wastewater.