Previous studies have suggested that whey supplementation may have beneficial effects on lipid profiles, although results were inconsistent. A literature search was performed in March 2015 for randomized controlled trials observing the effects of whey protein and its derivatives on circulating levels of triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). A meta-analysis was subsequently conducted. The meta-analysis results of 13 trials showed that whey supplementation significantly reduced the circulating TG level by 0.11 mmol/l (95% CI: -0.21, 0 mmol/l), whereas the whey protein had no effects on circulating TC (-0.11 mmol/l, 95% CI: -0.27, 0.05 mmol/l), LDL-C (-0.08 mmol/l, 95% CI: -0.23, 0.07 mmol/l) and HDL-C (0.01 mmol/l, 95% CI: -0.04, 0.05 mmol/l). Subgroup analysis showed that significant TG reduction disappeared in participants with low body mass index, low supplemental whey dose or under exercise training/energy restriction during the trial. No evidence of heterogeneity across studies and publication bias was observed. In conclusion, our findings demonstrated that the effects of whey protein supplementation were modest, with an overall lowering effect on TG but no effect on TC, LDL-C and HDL-C.