The present invention relates to methods for treatment and/or prevention of acute as well as chronic graft-versus-host-disease (GVHD), and in particular to methods for decreasing mortality and increasing especially long term survival; acute complications associated with GVHD such as diarrhea, weight loss and sepsis based on normalization of gut, liver, lung and skin microbiota and mucosal defense; rebalance of the immune system with normalization of cytokine production of IFN-γ, TNF-α, 11-4, IL-5, IL-6, IL-8, IL-9, IL-10 and IL-13 and prevention and/or treatment of cytokine storm; chronic complications associated with GVHD such as bronchiolitis obliterans and scleroderma, the method comprising oral, subcutaneous, intrapulmonary and/or dermal/transdermal administration of one or more mammalian defensins selected from the group of α- and β-defensins in a patient that has or is about to receive an allogeneic hematopoietic stem cell transplantation.