Oats are recognized to provide many health benefits that are mainly associated with its dietary fibre, β-glucan. However, the protein derived from oats is largely understudied with respect to its ability to maintain health and attenuate risk factors of chronic diseases. The goal of the current study was to investigate the metabolic effects of oat protein consumption in lieu of casein as the protein source in high fat, high sucrose (HF/HS) fed Wistar rats. Four-week-old rats were divided into three groups and were fed three different experimental diets: a control diet with casein as the protein source, a HF/HS diet with casein or a HF/HS diet with oat protein for 16 weeks. Heart structure and function were determined by echocardiography. Blood pressure measurements, an oral glucose tolerance test, and markers of cholesterol metabolism, oxidative stress, inflammation and liver function were also performed. Our results indicate that incorporation of oat protein in the diet was effective in preserving systolic heart function in HF/HS fed rats. Oat protein significantly reduced serum total- and LDL-cholesterol levels. Furthermore, oat protein normalized liver HMG-CoAR activity, which to our knowledge, is the first time this has been reported in the literature. Therefore, our research suggests that oat protein can provide hypocholesterolemic and cardioprotective benefits in a diet-induced model of metabolic syndrome.