Akkermansia muciniphila (Akk) has gained significant attention for its role in regulating metabolic health and its impact on diseases such as cancer, diabetes, obesity, and inflammatory bowel disease (IBD). Studies suggest that the regulatory effects of Akk are primarily realized through its secreted extracellular vesicles (Akk-EVs), rather than relying solely on the in vivo form. These highly stable bilayer vesicles can regulate physiological and pathological processes in host cells through local or systemic signaling. Unlike direct delivery by live bacteria, Akk-EVs can efficiently deliver a variety of bioactive molecules involved in the regulation of glucose metabolism, lipid homeostasis, intestinal immunity, and maintenance of intestinal barrier integrity without the risk of infection. Given that natural and engineered EVs are increasingly entering clinical trials, Akk-EVs, with their superior stability and specificity, present a promising therapeutic alternative to live bacterial treatments. This review summarizes the regulatory mechanisms of Akk-EVs in health and disease and discusses their potential applications in precision medicine and clinical therapy, offering new insights into therapeutic strategies for metabolic disorders, cancer, and gut diseases.