The use of algaecides to control high-density cyanobacterial blooms is often complicated by secondary pollution and the toxicity to non-target organisms. This study investigates the individual and combined effects of sodium dichloroisocyanurate (NaDCC, 5, 50, and 100 mg/L) and isothiazolinone (0.1, 0.5, and 1.5 mg/L) on a cyanobacteria-Vallisneria natans-microbe aquatic ecosystem, focusing on their interactions and ecological impacts. Results indicate that NaDCC could achieve a higher algae removal rate than isothiazolinone within 15 days, but has a greater negative effect on Vallisneria natans. Both algaecides disrupt nutrient and secondary metabolite balances at low and high concentrations, increasing nutrient loads and harmful substances. Optimal results were obtained with low concentrations of NaDCC (5 mg/L) and isothiazolinone (0.1 mg/L), effectively controlling cyanobacteria while minimizing harm to Vallisneria natans and reducing nutrient loads and microcystin accumulation. Algaecide application enhanced microbial diversity in water and leaves, shifting the dominant community from cyanobacteria to organisms adapted to the post-cyanobacterial decay environment. Metabolomic analysis indicated increased secretion of lipids and organic acids by cyanobacteria in response to algaecide stress. High concentrations of NaDCC and isothiazolinone disrupted nitrogen metabolism in cyanobacteria and induced ROS overproduction, affecting unsaturated fatty acid synthesis and other metabolic pathways. These findings highlight the importance of exploring different combinations of algaecides to reduce their concentrations, balance algal control with ecological stability, and offer insights for effective eutrophication management.