Background: The present study aimed to investigate the effects of fish oil supplements compared to corn oil on serum lipid profiles by performing a meta-analysis of randomized controlled trials (RCTs). Methods: Online databases including PubMed, Web of Science, and Scopus were searched until 30 December 2022. Pooled effect sizes were reported as the weighted mean difference (WMD) with 95% confidence intervals (CI). The Cochrane Collaboration's risk-of-bias tool was utilized to evaluate the quality of the studies. Lipid parameters, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL), were assessed in the meta-analysis. Results: Overall, 16 eligible trials were included in this systematic review and meta-analysis. The results revealed that the fish oil supplements significantly reduced TG (WMD: − 25.50 mg/dl, 95% CI: − 42.44, − 8.57, P = 0.000) levels compared to corn oil. Also, in this study, fish oil supplements had a positive and significant effect on HDL (WMD: 2.54 mg/dl, 95% CI: 0.55, 4.52). There were no significant changes in TC and LDL. Conclusions: Our findings showed the effects of fish oil supplements on reducing TG and increasing HDL-c compared to corn oil. Further larger and well-designed RCTs are required to confirm these data. [ABSTRACT FROM AUTHOR]