Background and Aim: Childhood and adolescent obesity is on the rise and is associated with chronic inflammation and elevated levels of inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6). This meta-analysis was conducted to examine the effect of aerobic exercise on CRP and IL-6 in overweight and obese children and adolescents. Material and Methods: A comprehensive literature search was conducted up to March 10, 2025 in databases including PubMed, Web of Science, Scopus, Google Scholar, Magiran, NoorMags, and Sid. The effect size was calculated using the weighted mean difference (SMD) and 95% confidence intervals with the CMA2 software. Results: IN total,15 studies (comprising 18 aerobic exercise interventions) involving 551 overweight and obese children and adolescents were included in the meta-analysis.The results showed that aerobic exercise interventions led to a reduction in CRP levels compared to the control group, approaching statistical significance (SMD = -0.433, 95% CI: -0.867 to 0.001, P = 0.050). However, aerobic exercise had a non-significant effect on IL-6 levels compared to the control group (SMD = -0.468, 95% CI: -1.268 to 0.332, P = 0.251). Conclusion: Aerobic exercise interventions in overweight and obese children and adolescents resulted in a statistically significant reduction in CRP levels, while changes in IL-6 were not significant, suggesting a limited impact of these interventions on inflammatory markers and underscoring the need for longer-term and combined intervention strategies.