Background: The hypothesis that long term supplemental preloads of whey protein concentrate (WPC) and soy protein isolate (SPI) 30 min before the largest meal, will improve blood pressure (BP), fasting blood sugar (FBS) and lipid profile of overweight and obese men in their in free living condition was tested. Methods: Forty - five men of 52, BMI = 25–40 kg/m2, after random allocation in WPC (n = 26) or SPI (n = 19) groups, drank 65 gr WPC or 60 gr SPI dissolved in 500 ml water 30 min before their ad libitum lunch for 12 weeks. Lipid profile and FBS were assessed before and after the study. Systolic and diastolic BP were measured before and after the study and every two weeks. Results: After 12 weeks, mean changes between the groups were significant for SBP (p < 0.02), DBP (p = 0.001), apo A-I, apo B (p < 0.001), LDL (p = 0.015), HDL (p = 0.017). Within group mean changes of WPC were significant for reduction of DBP, FBS, apo B, VLDL, LDL, TG (p < 0.001), SBP, TC (p = 0.001), and for increase of apo A-I (p < 0.001) and HDL (p = 0.001) relative to baseline. In SPI group, mean changes were significant relative to baseline for decrease of SBP (p < 0.02), DBP (p = 0.001), apo B (p < 0.001), LDL (p = 0.015) and for increase of apo A-I (p < 0.001) and HDL (p = 0.017). Conclusion: According to this study, WPC preloads at 30 min before ad libitum main meal, exert stronger beneficial effects than SPI preloads on BP, FBS and lipid profile of free living overweight and obese men after 12 weeks. Trial registration: Iranian Registry of Clinical Trials: IRCT201109062365N3.