Research indicates that bitter melon could be useful in the management of dyslipidemia. Still, there is disagreement concerning the findings. This systematic study was undertaken to clarify the impact of consuming bitter melon on lipid profile. The databases Web of Science, Cochrane Library, PubMed, and Scopus were queried from inception until February 9, 2023. The study assessed triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. The effect sizes were calculated using weighted mean differences (WMDs) and 95% confidence intervals (CIs). Eight randomized controlled trials (RCTs) with a total of 423 participants were included. Bitter melon consumption resulted in a significant decrease in plasma concentrations of TC (WMD; -9.71 mg/dL; CI: -17.69 to -1.74, p = 0.01) and TG (WMD; -10.24 mg/dL; CI: -19.92 to -0.56, p = 0.03), while bitter melon did not significantly lower blood LDL-C (WMD; -8.66 mg/dL; CI: -19.83 to 2.50, p = 0.12) and HDL-C concentrations (WMD; 0.54 mg/dL; CI: -2.38 to 3.45, p = 0.71). Subgroup analysis showed a significant decrease in TC and LDL-C and an increase in HDL-C at a dose of ≤ 2000 mg/day and an intervention period of ≤ 8 weeks. Also, the greatest impact of LDL-C and HDL-C was seen in diabetic and prediabetic people. Bitter melon supplementation positively impacts TC and TG levels. The limitations of this study were short-term trials (less than 3 months).