Resveratrol is a polyphenol with a well-established beneficial effect on dyslipidemia and hyperuricemia in preclinical experiments. Nonetheless, its efficacy and dose-response relationship in clinical trials remains unclear. This study examined whether resveratrol supplement improves the serum lipid profile and other metabolic markers in a dose-response manner in individuals with dyslipidemia. A total of 168 subjects were randomly assigned to placebo ( = 43) and resveratrol treatment groups of 100 mg/d ( = 41), 300 mg/d ( = 43), and 600 mg/d ( = 41). Anthropometric and biochemical parameters were analyzed at baseline and 4 and 8 weeks. Resveratrol supplementation for 8 weeks did not significantly change the lipid profile compared with the placebo. However, a significant decrease of serum uric acid was observed at 8 weeks in 300 mg/d (-23.60 ± 61.53 μmol/L, < 0.05) and 600 mg/d resveratrol groups (-24.37 ± 64.24 μmol/L, < 0.01) compared to placebo (8.19 ± 44.60 μmol/L). Furthermore, xanthine oxidase (XO) activity decreased significantly in the 600 mg/d resveratrol group (-0.09 ± 0.29 U/mL, < 0.05) compared with placebo (0.03 ± 0.20 U/mL) after 8 weeks. The reduction of uric acid and XO activity exhibited a dose-response relationship ( for trend, <0.05). Furthermore, a marked correlation was found between the changes in uric acid and XO activity in the resveratrol groups ( = 0.254, < 0.01). Resveratrol (10 μmol/L) treatment to HepG2 cells significantly reduced the uric acid levels and intracellular XO activity. Nevertheless, we failed to detect significant differences in glucose, insulin, or oxidative stress biomarkers between the resveratrol groups and placebo. In conclusion, resveratrol supplementation for 8 weeks had no significant effect on lipid profile but decreased uric acid in a dose-response manner, possibly due to XO inhibition in subjects with dyslipidemia. The trial was registered on ClinicalTrials.gov (NCT04886297).