Frequent outbreaks of harmful cyanobacterial blooms and the cyanotoxins they produce not only seriously jeopardize the health of freshwater ecosystems but also directly affect the survival of aquatic organisms. In this study, the dynamic characteristics and response patterns of transcriptomes and gut microbiomes in gastropod Bellamya aeruginosa were investigated to explore the underlying response mechanisms to toxic cyanobacterial exposure. The results showed that toxic cyanobacteria exposure induced overall hepatopancreatic transcriptome changes. A total of 2128 differentially expressed genes were identified at different exposure stages, which were mainly related to antioxidation, immunity, and metabolism of energy substances. In the early phase (the first 7 days of exposure), the immune system may notably be the primary means of resistance to toxin stress, and it performs apoptosis to kill damaged cells. In the later phase (the last 7 days of exposure), oxidative stress and the degradation activities of exogenous substances play a dominant role, and nutrient substance metabolism provides energy to the body throughout the process. Microbiomic analysis showed that toxic cyanobacteria increased the diversity of gut microbiota, enhanced interactions between gut microbiota, and altered microbiota function. In addition, the changes in gut microbiota were correlated with the expression levels of antioxidant-, immune-, metabolic-related differentially expressed genes. These results provide a comprehensive understanding of gastropods and intestinal microbiota response to toxic cyanobacterial stress.