Background: Chronic kidney disease (CKD) patients on dialysis display a low-grade systemic inflammatory burden. Nutritional interventions designed to activate the cytoprotective nuclear factor erythroid-2-related factor 2 (Nrf2) and inhibit nuclear factor-kB (NF-κB) have been proposed to mitigate this burden. Several bioactive compounds have been investigated to achieve this, including propolis, a resin produced by Apis mellifera bees. Considering the safety and efficacy of propolis, it could be a strategy to benefit these patients. Still, there are no studies using propolis in patients with CKD on peritoneal dialysis (DP), and clinical studies to support this application are lacking. Hypothesis/purpose: The objective and novelty of the present study are to evaluate the effects of propolis supplementation on inflammatory markers in patients with CKD on PD. Study design: A longitudinal, double-blind, placebo-controlled trial with CKD patients on PD. Methods: The patients were randomised into two groups: propolis that received four capsules of 100 mg (400 mg/day), containing concentrated and standardised dry EPP-AF® Brazilian green propolis extract) or placebo, four capsules of 100 mg (400 mg/day), of magnesium stearate, silicon dioxide, and microcrystalline cellulose, for two months. Plasma levels of inflammatory cytokines, including tumour necrosis factor (TNF-α) and interleukin-6 (IL-6), were evaluated by ELISA. Quantitative real-time PCR analyses were performed to evaluate the transcriptional expression levels of Nrf2 and NF-κB in peripheral blood mononuclear cells (PBMCs). Plasma malondialdehyde (MDA) levels, a lipid peroxidation marker, was measured as thiobarbituric acid reactive substances (TBARS). Routine biochemical markers, including C-reactive protein (CRP), were analysed using commercial kits. Carotid Intima-Media Thickness (CIMT) was measured with a doppler ultrasonography device. The study was registered on ClinicalTrials.gov under the number NCT04411758. Results: A total of 19 patients completed the study, ten patients in the propolis group (54 ± 1.0 years, five men, 7.2 (5.1) months on PD) and 9 in the placebo group (47.5 ± 15.2 years, three men, 10.8 (24.3) months on PD). The plasma levels of TNF-α reduced significantly (p = 0.02), and expression of Nrf2 showed a trend to increase (p = 0.07) after propolis supplementation. Conclusion: EPP-AF® Green Propolis extract (400 mg/day) supplementation for two months appears as a potential strategy to mitigate inflammation, reducing TNF-α plasma levels in CKD patients on PD.