Introduction: The use of medicinal plants have been increasing progressively around the world and been associated with decreasing Total Cholesterol (TC) and Low-Density Lipoprotein- Cholesterol (LDL-C) and, increasing High-Density Lipoprotein-Cholesterol (HDL-C) in humans. Ilex paraguariensis, known as yerba mate, is rich in bioactive compounds, especially chlorogenic acid has been shown as one of the major contributor to hypocholesterolemic. This review aimed to demonstrate if Ilex paraguariensis supplementation is more effective than placebo on lipid profile in randomized placebo-controlled trial. Methods: A careful search was performed in PubMed, Web of Science, Scielo, Scopus and Cochrane Library, published until May 2020. The following keywords of Medical Sub Headings (MeSH) were used as search terms: (“yerba mate” OR “Ilex paraguariensis”) AND (“dyslipidemia” OR “hyperlipidemia”) AND (“clinical trial” OR “Randomized Controlled Trial (RCT)” OR “randomly”). Results: The literature search identified 149 “Ilex paraguariensis x clinical trials”, 16 full-text assessed. After, following the inclusion and exclusion criteria, only 3 studies were chosen to qualitative and quantitative synthesis. The study showed that Ilex paraguariensis could improve HDL-C, but with no differences in TC and triglycerides, comparing to placebo-controlled group. Conclusion: The three included clinical trials have demonstrated high quality, low bias and HDL-C statistically different. To validate the last result, more clinical trials interventions are necessary, Although TC and triglycerides did not demonstrated differences statistically and increasing HDL-C may improve or protect the metabolism of lipid profile, after been supplemented by Ilex paraguariensis, compared to placebo-controlled trial.