© 2020 National Kidney Foundation, Inc. Objective: The objective of the study was to evaluate associations among diet quality, serum uremic toxin concentrations, and the gut microbiota profile in adults undergoing hemodialysis therapy. Design and Methods: This is a cross-sectional analysis of baseline data from a clinical trial involving adults receiving hemodialysis therapy. Usual dietary intake was determined using a diet history method administered by Accredited Practising Dietitians. Two approaches were used for diet quality assessment: (1) using three a priori defined plant-based diet indices—an overall plant-based diet index (PDI), a healthy PDI, and an unhealthy PDI and (2) classification of food group intake. Serum uremic toxins (p-cresyl sulfate and indoxyl sulfate (IS); free and total) were determined by ultra-performance liquid chromatography. Gut microbiota composition was established through sequencing the 16S rRNA gene in stool samples. Results: Twenty-two adults (median age 70.5 [interquartile range: 59-76], 64% male) were included in the final analysis. Higher adherence to the PDI was associated with lower total IS levels (P =.028), independent of dialysis adequacy, urinary output, and blood albumin levels. In contrast, higher adherence to the unhealthy PDI was associated with increases in both free and total IS. Several other direct and inverse associations between diet quality with uremic toxins, microbial relative abundances, and diversity metrics were also highlighted. Diet-associated taxa showed significantly different trends of association with serum uremic toxin concentrations (P <.05). Higher adherence to the PDI was negatively associated with relative abundances of Haemophilus and Haemophilus parainfluenzae that were related to elevated total IS levels. In contrast, increased intake of food items considered unhealthy, such as animal fats, sweets and desserts, were associated with bacteria linked to higher IS and p-cresyl sulfate (total and free) concentrations. Conclusions: The quality of diet and food selections may influence uremic toxin production by the gut microbiota in adults receiving hemodialysis. Well-designed dietary intervention trials that adopt multi-omic technologies appropriate for the functional annotation of the gut microbiome are needed to validate our findings and establish causality.