Acrolein is the main toxic metabolite of Ifosfamide (IFO) that causes urothelial damage by oxidative stress and in ammation. Here we investigate the molecular mechanism of action of gingerols, Zingiber o cinale bioactive molecules, as an alternative treatment for ifosfamide-induced hemorrhagic cystitis. Female Swiss mice were randomly divided into 5 groups: control; IFO; IFO + Mesna; and IFO + [8]-or [10]gingerol. Mesna (80 mg/kg, i.p.) was given 5 minutes before, 4 and 8 hours after IFO (400mg/kg, i.p.).Gingerols (25 mg/Kg, p.o.) were given 1 hour before and 4 and 8 hours after IFO. Animals were euthanized 12 hours after IFO injection. Bladders were submitted to macroscopic and histological evaluation. Oxidative stress and in ammation were assessed by malondialdehyde (MDA) or myeloperoxidase assays, respectively. mRNA gene expression was performed to evaluate Mesna and gingerols mechanisms of action. Mesna was able to protect bladder tissue by activating NF-κB and NrF2 pathways. However, we demonstrated that gingerols acted as an antioxidant and anti-in ammatory agent stimulating the production of IL-10, which intracellularly activated JAK/STAT/FOXO signaling pathway.