By adding four amendments, sodium silicate, sepiolite, quicklime, and monocalcium phosphate, the effects on the microbial community structure and microbially mediated nitrogen cycling functions of cadmium-copper co-contaminated soils were systematically investigated. The results showed that amendment application significantly increased soil pH while markedly reducing the contents of available cadmium and copper in the soil. Among the amendments, quicklime exhibited the strongest effect, decreasing the mass fractions of available cadmium and copper to 0.02 and 0.43 mg/kg, respectively, and increasing soil pH by 1.57 compared with the control. And, amendment application enhanced soil carbon and nitrogen nutrient levels and increased the expression of Cd2+- or Cu2+-transport-related proteins, potentially facilitating microbial adaptation to combined cadmium-copper stress. Sepiolite and sodium silicate treatments decreased the relative abundance of Proteobacteria while increasing those of Acidobacteriota and Chloroflexi, whereas quicklime treatment reduced the relative abundance of Acidobacteriota and increased those of Firmicutes and Bacteroidota. Both quicklime and monocalcium phosphate enhanced nitrogen fixation and denitrification functions, whereas sodium silicate and sepiolite exhibited inhibitory effects on the denitrification process. Overall, different amendments influenced nitrogen cycling processes in cadmium-copper co-contaminated soils at multiple levels by regulating microbial community structure and function.