Organ fibrosis is a serious health challenge worldwide, and its global incidence and medical burden are increasing dramatically each year. Fibrosis can occur in nearly all major organs and ultimately lead to organ dysfunction. However, current clinical treatments cannot slow or reverse the progression of fibrosis to end-stage organ failure, and thus advanced anti-fibrotic therapeutics are urgently needed. As a type of naturally derived nanovesicle, native extracellular vesicles (EVs) from multiple cell types (, stem cells, immune cells, and tissue cells) have been shown to alleviate organ fibrosis in many preclinical models through multiple effective mechanisms, such as anti-inflammation, pro-angiogenesis, inactivation of myofibroblasts, and fibrinolysis of ECM components. Moreover, the therapeutic potency of native EVs can be further enhanced by multiple engineering strategies, such as genetic modifications, preconditionings, therapeutic reagent-loadings, and combination with functional biomaterials. In this review, we briefly introduce the pathology and current clinical treatments of organ fibrosis, discuss EV biology and production strategies, and particularly focus on important studies using native or engineered EVs as interventions to attenuate tissue fibrosis. This review provides insights into the development and translation of EV-based nanotherapies into clinical applications in the future.