The efficient biological treatment of saline wastewater has been limited by the low activities of microorganisms under saline conditions. High salinity poses unbalance osmotic stress across the cell wall and even leads to cell plasmolysis. In this work, we aim to isolate salt-tolerant bacterial strains from activated sludge, and apply them for degrading chemical oxygen demand (COD) of saline organic wastewater. Two salt-tolerant strains were screened and isolated from activated sludge, which was domesticated with salty water for over 300 days. The two strains were identified as Bacillus cereus (strain A) and Bacillus anthracis (strain B) through 16S rRNA sequencing. The degradation characteristics of strain A were explored. The results showed the relative membrane permeability of strain A remained stable under high salt stress, which glycine and proline play an important role to maintain cell osmotic. The protein and soluble sugar amounts of strain were increased by higher salt concentrations. In simulating saline wastewater, the optimum culture temperature, pH, salinity, influent COD concentration and inoculation amount of strain A were 35 °C, 9, 4%, 8000 mg L−1, 6%, respectively. Optimal conditions could provide guidance for the treatment of practical saline wastewater. The linear regression model of each impact factor built based on the result PB experiment revealed that cross-linking time has the most significant influence on COD removal for salt-tolerant strains. It will provide theoretical basis for biological treatment of saline organic wastewater.