A large number of people suffer from tissue injury and defect worldwide, which constitutes a critical challenge for regenerative medicine. During the complicated process of tissue repair and regeneration, immune response that involves many kinds of immune cells often concurrently exists and plays a significant role, thus providing a promising target for the development of therapeutic strategies. As a critical player in cell-cell communication, extracellular vesicles (EVs) are a cluster of nano-sized vesicles of different categories, which have been reported to possess favorable immunoregulatory potential, and participate in the process of tissue repair and regeneration. Furthermore, EVs can be engineered with genetic or chemical strategies for optimized performance as therapeutic mediators. Here, we provide an outline on the biology of EVs as well as the role of EVs in immune regulation, focusing on exosomes, microvesicles, and apoptotic vesicles. We further summarize the applications of EV-based therapies for tissue regeneration, with particular emphasis on the modulation of immune system. Also, we have discussed the construction strategies of engineered EVs and the immunomodulatory capability of engineered EVs as well as their therapeutic potential in tissue repair. This review will highlight the outstanding potential of EV-based therapeutic strategies for tissue repair and regeneration. Impact statement Extracellular vesicles (EVs) have been shown to possess potent immunomodulatory abilities and thus hold great therapeutic potential for regenerative medicine via immune modulation. Also, the development of engineering technology has provided a feasible tool for optimizing the performance of natural EVs. We hereby outline the current knowledge regarding the features of EVs and the construction strategies of engineered EVs as well as the immunomodulation effects of natural and engineered EVs. We also highlight the applications of EV-based therapies for tissue regeneration, with particular emphasis on the modulation of immune system.