Obesity is associated with severe, difficult to control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress in asthma, leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment. Using a mouse model of house dust mite (HDM) induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ), we investigated the effects of obesity and ROS on HDM induced airway inflammation, remodelling, and airway reactivity (AHR). Obese allergic mice showed increased lung tissue eotaxin, airway tissue eosinophilia, and AHR compared to lean allergic mice. MitoQ reduced airway inflammation, remodelling and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obese-allergic mice. Similar effects were observed with decyl triphosphonium (dTPP+), the hydrophobic cationic moiety of MitoQ lacking ubiquinone. HDM induced oxidative sulfenylation of proteins was increased particularly in HFD mice. While only MitoQ reduced sulfenylation of proteins involved in protein folding in the endoplasmic reticulum (ER), ER stress was attenuated by both MitoQ and dTPP+ suggesting the anti-allergic effects of MitoQ are mediated in part by effects if its hydrophobic dTPP+ moiety reducing ER stress. In summary, oxidative signalling is an important mediator of allergic airway disease. MitoQ, likely through reducing protein oxidation and affecting the UPR pathway, might be effective for the treatment of asthma, and specific features of obese asthma.