Background and Objectives: Acculturation is associated with excessive weight gain among immigrants to the U.S. Whether dietary factors mediate this association is unclear. This study aimed to examine whether overall diet quality or specific component(s) of diet quality mediate the association between acculturation and Body Mass Index (BMI) among Mexican American (MA) men and women. Material and Methods: This is a secondary data analysis using dietary intake data from 24-hour dietary recalls, measured height and weight, and self-reported acculturation from the National Health and Nutrition Examination Survey (NHANES) cycles 1999-2000 to 2011-2012. A total of 6848 MA adults (≥20 yrs) with reliable dietary recall status and body measures were included in the study. Path analyses was performed in Mplus with complex survey design effects adjusted. Results: HEI components of whole grains and sodium were found to play meditating roles in the acculturation-BMI association, and their effects on BMI were opposing [indirect effect were -0.01 (SE 0.00) and 0.02 (0.01), respectively]. In gender-specific analysis, sodium [0.01 (0.00)] was a significant mediator only in MA men; whereas, whole grains [-0.01 (0.00)] was a significant mediator only in MA women. Conclusions: HEI components of whole grains and sodium appeared to be significant dietary mediators in the acculturation-BMI association. Understanding the variations of dietary components and their relationship with acculturation as well as BMI is useful for developing dietary interventions and obesity reduction.