Display omitted •Sludge reduction via microbial metabolism without extra energy and resource inputs.•The sludge reduction strategy is environmentally sustainable.•Thermodynamics and stoichiometry on the sludge reduction strategy were discussed.•Sludge reduction was reviewed based on substrate allocation and energy conversion.•Opportunities and challenges for the sludge reduction strategy were presented. Sludge reduction via microbial metabolism does not require extra energy and resource inputs and thus merits attention as an alternative approach for sustainable wastewater treatment. This review presents a summary and analysis of the existing literatures on sludge reduction based on microbial metabolism, as well as interprets these sludge reduction mechanisms using bacterial thermodynamics and stoichiometry. Future efforts should be directed toward using advanced analytical techniques to further reveal sludge reduction mechanisms. The feasibility of coupling sludge reduction and nutrient removal by microorganism metabolism needs to be further evaluated to minimize the effect of sludge reduction on nutrient removal. A comprehensive life cycle assessment of sludge reduction strategies is recommended to effectively confirm their sustainability. Full-scale research is needed to verify the results obtained from bench- and pilot-scale experiments. This review presents the future opportunities and challenges for sludge reduction based on microbial metabolism in the excess sludge disposal.