Wastewater recycling is an effective way to reduce the fresh water supply and pollutant discharge for industry. Nevertheless, wastewater recycling will inevitably lead to the accumulation of inorganic ions and organic pollutants, which can deteriorate the activated sludge system. A printing and dyeing wastewater (PDWW) recycling system was established in this study to investigate the mechanism of biological treatment system deterioration due to organic and inorganic pollutant accumulation. It was found that organic matter accumulation especially intermediate products of added dyes and auxiliaries is crucial for the biological treatment unit deterioration during the beginning of closed-loop PDWW recycling (first 40 days). In addition, inorganic salt accumulation, such as Ca²⁺, Na⁺, K⁺, SO₄^2- and Cl^-, can make it even worse afterwards. The results indicated that phenylalanine metabolism, synthesis and degradation of ketone bodies, butanoate metabolism and pyruvate metabolism were the four most significantly influenced metabolic pathways in the PDWW recycling system attributed to the organic matter accumulation. In addition, accumulated inorganic salts could inhibit glycan biosynthesis and metabolism, xenobiotic biodegradation and metabolism and lipid metabolic pathways in the PDWW recycling system, which ultimately deteriorated the biological treatment system.