Excess sludge production is one of the major challenges in the wastewater treatment plants worldwide. The main solution is to reduce the burden of sludge by lowering its production. In this study, the strategies for sludge reduction using uncoupler DNP (2,4-dinitrophenol) with diatomite or diatomaceous earth (natural sedimentary rock) are evaluated for practical application using cost analysis and assessment of environmental impact. There was a decrease in average removal efficiency of chemical oxygen demand (COD), ammonia nitrogen (NH 4 + -N) and total nitrogen (TN) of 7–30%, 20% and 44%, respectively. The sludge volume index (SVI) was 80–120 mL/g while the sludge activity increased by 21%. By cost analysis and comparison of the various parameters, it was determined that the optimal dosage of DNP was 6 mg/L. The problem of poor effluent quality and sludge performance caused by the addition of DNP alone was solved by the collaborative addition of DNP and diatomite. Diatomite can absorb the coupling agent like a carrier to form a compound uncoupling agent. Diatomite easily aggregate and mixed with sludge micelle particles. DNP will slowly release and dissolve into sludge micelles after they are mixed, resulting in higher DNP concentration in sludge micelles. A synergistic effect of DNP and diatomite on sludge reduction showed increase in removal efficiency COD, NH 4 + -N and TN of 13.35%, 18.6% and 26.58%, respectively. SVI was decreased by 13%. A sewage treatment of 1 m 3 can still save sludge treatment cost by $ 0.0084. Comparing the synergistic dose, observed sludge yields (Yobs) decreased by 28.28% (48 mg of DNP with 0.4 g of diatomite; one-time dosage per two-days) and 21% (24 mg of DNP with 0.2 g of diatomite; once a day dosage). The sludge activity also increased. By orthogonal test results, the optimum environmental influence factors for the treatment system are set to 25 °C and pH 7.