Background <p>Childhood obesity has a rising prevalence, and the function of oxidative stress is of increasing interest. However, few studies are available on the association of composite dietary antioxidant index (CDAI) with childhood obesity. Therefore, this study intends to investigate the relationship between CDAI and childhood obesity, and to further examine the potential mediating role of the systemic immune-inflammation index (SII) on this association.</p> Methods <p>Using data from the National Health and Nutrition Examination Survey (NHANES) 2011–2018, restricted cubic spline (RCS) and logistic regression analyses were performed to explore the relationships of CDAI, SII, and childhood obesity. Additionally, mediation analysis was used to determine the mediating role of SII.</p> Results <p>We finally included 4,134 participants, with an obesity rate of 29.05%. The fully adjusted regression model showed a significant inverse relationship between CDAI and childhood obesity (OR 0.93; 95% CI 0.89–0.97, <i>P</i> = 0.001). The RCS analysis found a linear association between the two (P for nonlinear = 0.816). Mediation analysis results indicated that the proportion mediated by SII was 15.46% in the association between CDAI and obesity in children and adolescents.</p> Conclusions <p>An association exists between CDAI and childhood obesity, with SII acting as a partial mediator.</p>