Background: The gut microbiota and its metabolites are essential for host health and dysbiosis has been involved in several pathologic conditions such as type 2 diabetes (T2D) and cardiovascular disease (CVD). Recent studies have identified that plasma imidazole propionate (ImP), a microbial-produced metabolite, is increased in patients with prediabetes and T2D. More recently, ImP was found to be significantly increased in patients with overt CVD. Here, we aimed to investigate the association between ImP and CVD risk factors: blood pressure, HDL-cholesterol, LDL-cholesterol and insulin-resistance in overweight and obese subjects without T2D or use of any metabolic diseases-related medication. Methods: Plasma metabolites, including ImP, were determined in 107 male or post-menopausal women with overweight/obesity, but without T2D. Insulin-sensitivity was assessed with the gold standard method: the hyperinsulinemic-euglycemic clamp using the isotope [6,6-2H2] glucose and expressed as glucose rate of disposal (Rd) for peripheral insulin sensitivity and suppression of endogenous glucose production (EGP) for hepatic insulin sensitivity. Results: Partial correlation analysis controlled for BMI and age showed a significant correlation between ImP and diastolic blood pressure (rs = 0.285, p = 0.004) and a borderline significance with systolic blood pressure (rs = 0.187, p = 0.060); however, systolic and diastolic blood pressure did not correlate with ImP precursor histidine (rs = 0.063, p = 0.526 and r = −0.038, p = 0.712, respectively). We did not find a correlation between ImP with LDL-cholesterol or HDL-cholesterol (rs = −0.181, p = 0.064 and rs = 0.060, p = 0.546, respectively). Furthermore, there was no association between plasma ImP concentrations and Rd and EGP suppression. Conclusion: In this cohort with overweight/obese subjects without T2D, plasma ImP concentrations were positively correlated with diastolic blood pressure but not with insulin-sensitivity.