ABSTRACT: The objective was to evaluate the effects of 6 months of supplementation with Altilix®, containing chlorogenic acid and its derivatives, and luteolin and its derivatives, on cardiovascular risk and hepatic markers in subjects with metabolic syndrome (MetS). A randomized, double-blind, placebo-controlled study was performed in 100 subjects with MetS with a follow-up period of 6 months; 50 subjects were randomized to Altilix® (26 men and 24 women, mean age 63 ± 8 years) and the other 50 to placebo (28 men and 22 women, mean age 63 ± 11 years). Anthropometric, cardiometabolic, and hepatic parameters were assessed at baseline and at the end of follow-up. Carotid intima-media thickness and endothelial function were assessed by doppler ultrasound and by flow-mediated dilation of the brachial artery, respectively. The presence and degree of non-alcoholic fatty liver disease (NAFLD) was assessed by the fatty liver index (FLI), and subjects were divided into three subgroups: (1) without NAFLD; (2) with borderline NAFLD; and (3) with NAFLD. After 6 months of Altilix® supplementation, we found a significant improvement vs. placebo in most of the evaluated parameters, including body weight (-2.40% (95% CI -3.79, -1.01); p < 0.001), waist circumference (-2.76% (95% CI -4.55, -0.96); p = 0.003), HbA1c (-0.95% (95% CI -1.22, -0.67); p < 0.001), plasma lipids, FLI (-21.83% (95% CI -27.39, -16.27); p < 0.001), hepatic transaminases, flow-mediated dilation (10.56% (95% CI 5.00, 16.12); p < 0.001), and carotid intima-media thickness (-39.48% (95% CI -47.98, -30.97); p < 0.001). Further, the improvement in cardiometabolic variables was independent of the degree of hepatic steatosis. Altilix® supplementation improved hepatic and cardio-metabolic parameters in MetS subjects. Altilix® supplementation was a beneficial approach in the management of hepatic and cardiometabolic alterations in MetS subjects.