Chronic kidney disease (CKD) is one kind of illness with abnormal renal structure and function caused by many factors. Probiotics can be used to regulate intestinal microflora and enhance intestinal mucosal barrier, thus, intervention with probiotics may be regarded as one of the potential ways to protect against CKD. In vitro and in vivo experiments showed that Lactiplantibacillus plantarum MA2 (MA2), a probiotic separated from traditional Chinese Tibetan kefir grains, could degrade the uremic toxins including creatinine, urea nitrogen and uric acid. Oral administration of MA2 or its inactive strains (IMA2) could decrease serum uremic toxins of adenine-induced CKD mice, and also elevate the relative expression of claudin-1. Meanwhile, intervention of MA2 or IMA2 decreased the contents of lipopolysaccharide, Toll-like receptor 4 (TLR4) and interleukin-1β (IL-1β) in the kidney. 16S rDNA sequencing results indicated that the intervention of MA2 or IMA2 regulated the gut microbiota structure by elevating the abundance of Lactobacillus, and decreasing the abundance of Proteobacteria. Thus, oral administration of MA2 or IMA2 can reduce the uremic toxins in CKD mice by regulating gut microflora and restoring the intestinal mucosal barrier. Our study provided a theoretical basis for the application of MA2 and its postbiotics in the CKD intervention and treatment.