Abstract This study investigated the biogas (hydrogen and methane) production and microbial community dynamics in the anaerobic treatment of saline industrial effluents containing mono-ethylene glycol (MEG) as a major pollutant. An immobilized sludge anaerobic baffled reactor (ISABR) inoculated with salt-adapted mixed culture was developed as a lab-scale experiment, and effects of operational conditions (e.g., salinity, organic loading rates (OLRs), and temperature) on the system performance were examined. First, different OLRs of 0.64–2.34 gCOD/L/d, by increasing the initial MEG concentrations at a fixed hydraulic retention time (HRT) of 4.5 d, were examined from day 1 to 100 at lower salinity of 10 gNaCl/L and ambient temperature (25 ± 6 °C). Under such operational conditions, maximum methane yield (MY) of 165 mL CH4/gCODadd and hydrogen yield (HY) of 102 mL H2/gCODadd were achieved at the lowest OLR of 0.64 gCOD/L/d. Afterwards, impacts of higher salinities of 15–25 gNaCl/L were investigated from day 101 to 208 at a controlled mesophilic temperature of 35 °C and fixed OLR (0.64 gCOD/L/d). As a result, enhanced HY and MY (∼2-fold) at elevated salinities up to 25 gNaCl/L were obtained. Moreover, the compartment-wise water and gas analyses, for both experiments, revealed that hydrogen and methane peaked in former and latter compartments, respectively, and the peak location shifted depending on overall imposed OLR. The relative abundance of dominant salt-tolerant bacterial genus Desulfovibrio increased when OLR and operational temperature were increased, while dominant archaeal genera responded substantially when temperature was increased. Economic feasibility of ISABR for bioenergy recovery and treatment of MEG was evaluated by a cost-benefit analysis, suggesting that salinity level along with suitable operational temperature substantially affects the maximum net profit.