Objective This study aims to elucidate the effects of oral nutritional supplements on inflammatory factors and antioxidant status in patients undergoing hemodialysis through a meta-analysis of previous research. Methods This study conducted literature databases from inception to November 2024, including PubMed, Embase, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI), to identify all published randomized controlled trials assessing the impact of oral nutritional supplementation on inflammation and oxidative stress in patients on maintenance hemodialysis. Heterogeneity was assessed using the Chi-square test. Subgroup analyses and sensitivity analyses were performed to explore the sources of heterogeneity. Publication bias was evaluated using funnel plots and the Egger test. Results Supplementation with unsaturated fatty acids did not significantly affect serum CRP levels in patients undergoing hemodialysis (MD = - 0.93, 95% CI [- 2.53, 0.68], Z = 1.13, P = 0.26). The total antioxidant capacity in the antioxidant group was higher than that in the control group (MD = 0.09, 95% CI [0.05, 0.14], Z = 4.41, P < 0.0001). The MDA levels in the antioxidant group were lower than those in the control group (MD = - 2.28, 95% CI [- 2.75, - 1.80], Z = 9.42, P < 0.0001), while the difference in IL-6 levels between the antioxidant group and the control group was not statistically significant (MD = - 0.10, 95% CI [- 0.56, 0.36], Z = 0.41, P = 0.68). Conclusion Unsaturated fatty acids do not have a significant effect on serum CRP levels in patients undergoing hemodialysis. The antioxidants (vitamin E and polyphenols) can enhance the antioxidant capacity and reduce MDA levels in these patients; however, their impact on IL-6 levels is not significant. Further high-quality randomized controlled trials are needed to validate these conclusions.