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Dyslipidemia/hyperlipidemia are among the risk factors for chronic diseases, especially cardiovascular diseases. Red Yeast Rice (RYR) herbal supplement may be helpful in improving serum fat levels due to some mechanisms. Therefore, the aim of this study was to evaluate the effects of RYR consumption on total serum cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels in adults. Four comprehensive databases (SCOPUS, PubMed/MEDLINE, EMBASE, and Web of Science) were employed until 23 December 2021 RCTs, with 24 treatment arms included after screening 3623 articles. Pooled data showed significant effectiveness in lowering TC (WMD: −33.16 mg/dl, 95% CI: −37.69, −28.63, P < 0.001), LDL-C (WMD: −28.94 mg/dl, 95% CI: −32.90, −24.99, P < 0.001), and TG (WMD: −23.36 mg/dl, 95% CI: −31.30, −15.43, P < 0.001) concentration and increasing HDL-C concentration (WMD: 2.49 mg/dl, 95% CI: 1.48, 3.49, P < 0.001) following RYR supplementation. Furthermore, the effect of this herbal drug in doses less than 1200 mg and with an intervention duration of less than 12 weeks was more in individuals with dyslipidemia. In conclusion, this comprehensive article and meta-analysis showed that RYR significantly decreases TC, TG, and LDL-C as well as increases HDL-C. [ABSTRACT FROM AUTHOR]