<p>Mine wastewater pollution, primarily caused by heavy metals and sulfates, poses a significant threat to ecosystems and water quality in mining-affected regions. Effective remediation is essential for mitigating these environmental impacts and ensuring sustainable water management. This study explores the potential of bio-modified coal gangue (MCG) as a sustainable solution for remediating mine wastewater. Bio-modification significantly improved the gangue’s physicochemical properties, enhancing its adsorption capacity for both sulfates and heavy metals. Sulfate removal was primarily driven by microbial activity, with sulfate-reducing bacteria (SRB) in activated sludge and mine water producing removal efficiencies of up to 58.49%. Heavy metals, including mercury, antimony, copper, and arsenic, were effectively reduced to levels meeting regulatory standards, though additional treatment is required for zinc. Key factors influencing performance included temperature, pH, and particle size, with SRB-modified gangue in activated sludge demonstrating superior adaptability and stability across varying conditions. SEM analysis confirmed that bio-modification introduced surface roughness, porosity, and active sites essential for pollutant adsorption. These findings highlight the dual benefits of MCG in addressing wastewater treatment and coal gangue utilization, offering an innovative, cost-effective, and environmentally sustainable approach to mine wastewater remediation.</p>