To evaluate the associations between composite dietary antioxidant index (CDAI) and common non-communicable diseases (NCDs) and explore the potential effects of inflammatory indices in these associations. We included 20,097 adults from the National Health and Nutrition Examination Survey 2003-2018. Multivariable logistic regressions were applied to evaluate the associations between CDAI and common NCDs. Mediation analysis was used to explore the role of inflammatory indices in the associations. Higher CDAI was associated with a downward trend in the incidence of obesity, cardiovascular disease (CVD), chronic respiratory diseases, and chronic kidney disease (CKD) ( for trend < 0.05). The association between CDAI and CVD was influenced by C-reactive protein (CRP), red blood cell width (RDW), and neutrophil to lymphocyte ratio (NLR), with mediated proportions of 3.490%, 5.173%, and 2.351%, respectively. NLR partially contributed to the link between CDAI and CKD, with a mediating ratio of 2.746%. Additionally, we observed additive interactions between CDAI and CRP (RERI (95% CI): 0.282 (0.070, 0.494), AP (95% CI): 0.539 (0.088, 0.991), as well as RDW on CVD (RERI (95% CI): 0.318 (0.124, 0.511), AP (95% CI): 0.717 (0.217, 1.218)). There also appeared to be a weak multiplicative interaction between CDAI and RDW on CVD (-int = 0.049). Our investigation ascertained that CDAI was related to common NCDs. Moreover, inflammatory indices played an important role in the associations between CDAI and NCDs.