The artemisinin sustained-release algaecides (ASAs) have been proven to be a safe and effective mean of inhibiting cyanobacteria in laboratory experiments. However, their effectiveness and impacts on ecosystem functions (EF) in natural waters are still unclear. In this study, the in-situ inhibitory effect of ASAs on cyanobacteria in natural waters was investigated over a period of 110 days to assess EF impacts dominated by microbes and floating plants. The results indicated that ASAs had a long-term inhibitory effect on cyanobacteria. ASAs did not affect sediment but increased TOC and TP in the water column in 2-10 days. Microbial diversity and network analyses indicated that ASAs enhanced bacterial diversity, network complexity, and hub-bacteria in networks. Metabolic pathway predictions and CCA analysis showed that ASAs maintained the stability of EF by enhancing the metabolic capacities of bacteria, and the relationships between metabolic microorganisms and environmental factors. PLS-PM revealed that ASAs primarily drove bacterial resistance to cyanobacteria, which was the key mechanism for its long-term inhibition of cyanobacteria. However, the early outbreak of floating plants was not conducive to the long-term inhibition of cyanobacteria by ASAs. This study provides new insights into the mechanisms and ecological impacts of cyanobacterial inhibition by ASAs in complex aquatic environments.