The present study was conducted to determine the effect of shrimp protein concentrate on insulin resistance in a diet-induced obese mouse model. Male C57BL/6J mice fed a commercial high-fat diet (60 kcal% from fat) for 12 weeks were divided into three groups and then switched to a high-fat diet prepared in the lab. One group was used as the high-fat diet control and the other two were fed the high-fat diet with 35% or 70% of casein replaced by the same amount of protein from shrimp protein concentrate for 9 weeks. A group of age and sex matched C57BL/6J mice fed a low-fat diet (10% kcal from fat) all the time were used as the normal or low-fat diet control. Weekly body weight, daily food intake, weekly 4-hr fasting blood glucose, oral glucose tolerance and overnight fasting blood glucose, insulin and lipids were measured. It was observed that replacing dietary casein with shrimp protein significantly improved oral glucose tolerance and 4-hr fasting blood glucose levels while having no effect on the fasting blood glucose and insulin levels. There was a trend of increasing body weight and food intake, particularly at 35% replacement, which also increased blood total cholesterol levels while having no effect on triacylglycerol levels. There were mixed results of shrimp protein concentrate on metabolic phenotypes while a dramatic improvement in oral glucose tolerance was seen. Additional studies are required to verify the observed benefits and further look into the underlying mechanisms.