Abstract Background: The dietary inflammatory index (DII) has been associated with metabolic syndrome (MetS), but evidence for sex-specific effects with causal support and cross-national validation remains limited. Methods: We harmonised individual-participant data from 56,475 adults across US NHANES, Korean KNHANES, and Mexican ENSANUT using survey-weighted sex-stratified logistic regression. Three complementary approaches assessed the inflammatory pathway: CRP-based Mendelian randomization (primary: 84 female-matched instruments; sensitivity: 56-SNP sex-overlap subset), exploratory direct diet MR, and proxy gap decomposition. Country-specific population attributable fractions evaluated cross- cultural DII construct validity. Results: Observational analyses revealed a robust female-specific DII-MetS association (OR=1.15, P