Strategies for controlling cholesterol and lipid metabolism, including the use of food supplements, are part of the non-pharmacological intervention to ameliorate cardiovascular health. To demonstrate the efficacy of a standardized flavonoids (150 mg/day) extract from on cholesterol and lipid management, a placebo-controlled clinical trial on 64 subjects with high cholesterol was carried out. The total study duration was 4 months, with intermediate checkpoints at 1-month intervals. Low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) cholesterol, total cholesterol (TC) levels, oxidized low-density lipoprotein (ox-LDL), and paraoxonase activity (PON1) were measured as primary endpoints (efficacy evaluation), while weight, blood pressure, hepatic and renal function blood markers were measured as secondary endpoints (safety evaluation). After 4 months, both TC and LDL-C significantly decreased by 8.8% and 11.5%, respectively, along with a 5.5% increase in HDL-C which was trending towards significance. In addition, ox-LDL was significantly reduced by 2.0%, while PON1 was significantly increased by 6.5%. The secondary endpoints were not changed during the study, demonstrating a good tolerability of the test product. Our findings demonstrate the efficacy of the extract as a natural approach for cholesterol and lipid metabolism management.