Abstract: Over the past few years, the issue of Cyanobacteria bloom pollution has escalated due to the combined impacts of global warming and eutrophication in aquatic systems. This has resulted in the release of toxic microcystins (MCs), posing a significant threat to human health and aquatic ecosystems. Effectively controlling and eliminating MCs from water bodies is a pressing global challenge. Fortunately, prior research has demonstrated that microbial degradation of MCs presents an efficient and environmentally friendly solution. This review explores the production, structure, and toxicity of MCs, with a focus on summarizing global advancements in enzymatic degradation pathways, degradation enzymes, and degradation genes associated with MCs. Additionally, it also analyzes the potential applications of microbial degradation bacteria in the ecological restoration of water bodies. Furthermore, the paper delves into future research directions, including alternative pathways for non-mlr-mediated MCs degradation mechanisms, optimizing the expression of MCs-degrading enzymes, and constructing highly efficient dual-functional degradation bacteria. These perspectives aim to deepen human’s understanding of microbial degradation mechanisms of MCs and provide innovative solutions to address the global challenge of MCs contamination in water bodies.