Endothelial dysfunction is recognized as an early sign of systemic atherosclerosis, and it represents a therapeutic target to prevent long-term cardiovascular (CV) consequences. Alpha-lipoic acid (ALA) is a commonly used dietary supplement exerting anti-oxidant and anti-inflammatory effects. We investigated whether a three-month treatment with ALA improves endothelial function, as assessed by flow-mediated dilation (FMD) of the brachial artery, and clinical and metabolic risk factors in overweight/obese youths. We enrolled 67 overweight/obese children, and 22 normal-weight metabolically healthy controls. Overweight/obese youths were randomly allocated in a double-blinded manner to receive ALA (n = 34) or placebo (n = 33). Of these, 64 (32 ALA, 32 placebo) completed the follow-up. At baseline, in ALA and placebo groups, FMD was similar, but lower as compared with that in controls (p = 0.045). At three months, within the ALA and placebo groups, FMD did not change significantly. However, the basal and peak diameter of brachial artery significantly increased after ALA treatment as compared to placebo (p = 0.036 and p = 0.01, respectively). There were no significant within- and between-group changes for anthropometric and metabolic variables. The results show that ALA supplementation improves vascular tone and may have a beneficial effect on CV health in overweight/obese youths.