Background: The human gut microbiome (GM) has been observed to vary by race/ethnicity. Objective: Assess whether racial/ethnic GM variation is mediated by differences in diet. Design: Stool samples collected from 2013 to 2016 from 5267 healthy Multiethnic Cohort participants (age 59–98) were analyzed using 16S rRNA gene sequencing to estimate the relative abundance of 152 bacterial genera. For 63 prevalent genera (>50% in each ethnic group), we analyzed the mediation of GM differences among African Americans, Japanese Americans, Latinos, Native Hawaiians, and Whites by overall diet quality (Healthy Eating Index score (HEI-2015)) and intake amounts of 14 component foods/nutrients assessed from 2003 to 2008. For each significant mediation (p < 1.3 × 10−5), we determined the percent of the total ethnicity effect on genus abundance mediated by the dietary factor. Results: Ethnic differences in the abundance of 12 genera were significantly mediated by one or more of eight dietary factors, most frequently by overall diet quality and intakes of vegetables and red meat. Lower vegetable intake mediated differences in Lachnospira (36% in African Americans, 39% in Latinos) and Ruminococcus-1 (−35% in African Americans, −43% in Latinos) compared to Native Hawaiians who consumed the highest amount. Higher red meat intake mediated differences in Lachnospira (−41%) and Ruminococcus-1 (36%) in Native Hawaiians over African Americans, who consumed the least. Dairy and alcohol intakes appeared to mediate and counterbalance the difference in Bifidobacterium between Whites and Japanese Americans. Conclusions: Overall diet quality and component food intakes may contribute to ethnic differences in GM composition and to GM-related racial/ethnic health disparities.