Chronic kidney disease (CKD) can cause gut microbiota dysbiosis and thus impair intestinal barrier function. Disruption of intestinal homeostasis facilitates the production of enterogenic toxins, which exacerbate CKD-induced uremic toxicity and inflammation. Dietary fiber, by targeting the gut-kidney axis, could be used for CKD treatment. Psyllium seed husk (PSH) extracted from the seeds of Plantago ovata contains highly branched, gel-forming arabinoxylan. Positive effects of PSH on host physiology have been demonstrated but whether it also acts on the microbial ecosystem in CKD patients is unknown. In this study, the effects of dietary PSH on the gut microbiota, intestinal barrier function, systemic inflammation, uremic toxins, and renal injury were investigated in 5/6 nephrectomy (5/6Nx) CKD rats. Blood, feces, and kidney and colon tissues were collected from PSH-treated and control rats and subjected to biochemical and histological analyses, enzyme-linked immunosorbent assays, and 16SrRNA sequencing. PSH supplementation reduced serum creatinine and blood urea nitrogen levels, and attenuated renal tubular interstitial injury, in 5/6Nx rats. 16SrRNA sequencing showed that PSH improved the gut microbiota and intestinal barrier function in addition to down-regulating serum interleukin (IL)-1, IL-6, and indoxyl sulfate levels. Together, these results demonstrate the potential of PSH supplementation for treating CKD, including by improving intestinal microecology, reducing uremic toxin levels and systemic inflammation, and delaying disease progression.