Salinity stress affects the anaerobic digestion (AD) process and reduces methane production in most cases. This review described the occurrence and impacts of salinity from common substrates (e.g., food waste, organic wastewater and algae) in AD process, and elucidated the mechanisms by which salinity affects AD from the perspectives of microbial community, key genes and enzymes. Salinity in AD comes mainly from chemical additives in the substrate (e.g., salt in food waste) or from the substrate itself (e.g., saline algae). Low salinity can promote methane production, as appropriate Na+ concentrations can promote ATP synthesis and NADH oxidation, thus facilitating microbial metabolism. High salinity leads to lysis of salt-intolerant microbes, altering the microbial community and inactivating key enzymes, thereby blocking methanogenesis. Microbes can adopt “salt-in” and “compatible solute” strategies to resist salt stress. In addition, quorum sensing is also considered as a potential defense mechanism. Inspired by these cell survival mechanisms, the disinhibition strategies were elaborated from three aspects, namely front optimization (pretreatment, co-digestion, inoculum acclimation, dilution), process optimization (addition of osmoprotectants, potassium, conductive materials and other additives), and system optimization (bioelectrochemical enhancement). This review provides guidance for further studies on developing suitable mitigation strategies to enhance methane production under different salinity stress conditions.