Abstract Background and aims In patients with chronic kidney disease (CKD), alterations in gut microbiome are posited to be responsible for gastrointestinal symptoms and generation of p-cresol, a uremic toxin that has been associated with CKD progression and cardiovascular mortality. This pilot study investigated whether Probinul-neutro ® , a synbiotic that normalizes intestinal microflora, may lower plasma p-cresol concentrations and reduce gastrointestinal symptoms in non-dialyzed CKD patients. Methods and results This was a double-blind, randomized placebo-controlled trial. Thirty patients on 3–4 CKD stages were randomized to receive either Probinul neutro ® or placebo for 4 weeks. Total plasma p-cresol concentration was assessed at baseline, and 15 and 30 days after treatment start. At the same study times, ease and frequency of defecation, upper and lower abdominal pain, stool shape, borborygmi, and flatus were quantified by subjective assessment questionnaires. Compared to baseline total plasma p-cresol median concentrations on 15th and 30th day were significantly lower in patients receiving Probinul-neutro ® (2.31 and 0.78 vs. 3.05 μg/ml, p  < 0.05; n  = 18); no changes of plasma p-cresol concentrations were recorded in placebo-treated patients. No significant changes in gastrointestinal symptoms were observed during the study both in Probinul-neutro ® -treated and placebo-treated patients. Conclusion Probinul-neutro ® lowered total plasma p-cresol concentrations but did not ameliorate gastrointestinal symptoms in non-dialyzed CKD patients. Because high plasma concentrations of p-cresol in early phases of CKD are predictive of progression to end-stage renal disease, the results of our study suggest that synbiotics deserve attention as possible tools to delay CKD progression towards end-stage renal disease (ESRD). ClinicalTrials.gov identifier NCT02008331.