Type 2 diabetes is highly prevalent in North America and is associated with increased risk of cardiovascular disease (CVD). Evidence supports a role for soy protein in the reduction of serum lipids related to CVD risk; however, few studies have focused on adults with type 2 diabetes who are not on lipid-lowering medications and/or do not have diabetic complications. The purpose of this study was to determine the effect of soy protein isolate (SPI) consumption on serum lipids in adults with diet-controlled type 2 diabetes. Using a double-blind, randomized, crossover, placebo-controlled intervention study design, adults with diet-controlled type 2 diabetes (n = 29) consumed SPI (80 mg/d aglycone isoflavones) or milk protein isolate (MPI) for 57 d each separated by a 28-d washout period. Twenty-four-hour urine samples were collected on d 54-56 of each treatment for analysis of isoflavones and blood was collected on d 1 and 57 of each treatment and analyzed for serum lipids and apolipoproteins. SPI consumption increased urinary isoflavones compared with MPI. SPI consumption reduced serum LDL cholesterol (P = 0.04), LDL cholesterol:HDL cholesterol (P = 0.02), and apolipoprotein B:apolipoprotein A-I (P = 0.05) compared with MPI. SPI did not affect serum total cholesterol, HDL cholesterol, triacylglycerol, apolipoprotein B, or apolipoprotein A-I. These data demonstrate that consumption of soy protein can modulate some serum lipids in a direction beneficial for CVD risk in adults with type 2 diabetes.