Migrasomes are recently identified extracellular vesicles and organelles formed in conjunction with cell migration. They are situated at the rear of migrating cells, exhibit a circular or elliptical membrane-enclosed structure, and function as a new organelle. Migrasomes selectively sort intercellular components, mediating a cell migration-dependent release mechanism known as migracytosis and modulating cell-cell communication. Accumulated evidence clarifies migrasome formation processes and indicates their diverse functional roles. Migrasomes may also be potentially correlated with the occurrence, progression, and prognosis of certain diseases. Migrasomes' involvement in physiological and pathological processes highlights their potential for expanding our understanding of biological procedures and as a target in clinical therapy. However, the precise mechanisms and full extent of their involvement in immunity, barriers, and diseases remain unclear. This review aimed to provide a comprehensive overview of the roles of migrasomes in human immunity and barriers, in addition to providing insights into their impact on human diseases. STATEMENT OF SIGNIFICANCE: Migrasomes, newly identified extracellular vesicles and organelles, form during cell migration and are located at the rear of migrating cells. These circular or elliptical structures mediate migracytosis, selectively sorting intercellular components and modulating cell-cell communication. Evidence suggests diverse functional roles for migrasomes, including potential links to disease occurrence, progression, and prognosis. Their involvement in physiological and pathological processes highlights their significance in understanding biological procedures and potential clinical therapies. However, their exact mechanisms in immunity, barriers, and diseases remain unclear. This review provides an overview of migrasomes' roles in human immunity and barriers, and their impact on diseases.