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Context: Polyphenols have antioxidant, anti-inflammatory, and anti-glycation properties., Objective: To assess the effects of dietary polyphenols, from food sources or supplements, on the anthropometric, glycemic, renal, inflammatory, and oxidative stress markers in adults with diabetic nephropathy (DN)., Data Sources: Systematic searches for randomized clinical trials were performed in MEDLINE, Embase, CENTRAL, Web of Science, LILACS, SciELO, opengrey.eu, and ClinicalTrials.gov databases until December 2021., Data Extraction: Studies with adults with DN were included. Random-effects meta-analyses were conducted. Risk of bias of the studies and Grading of Recommendations, Assessment, Development, and Evaluation assessment were carried out., Data Analysis: The searches resulted in 5614 unique occurrences, and 34 full-text articles were retrieved. Of these, 17 studies were included in the qualitative synthesis. Most of the studies used soy protein or milk (n = 5; 0.5-1 g/kg of body weight/d of soy protein, or introduction of 240 mL/d of soy milk) or turmeric/curcumin (n = 5; dose range, 80 to 1500 mg/d) as the intervention. The following outcomes were analyzed: body mass index, glycated hemoglobin (HbA1c), proteinuria, creatinine clearance, glomerular filtration rate (GFR), urinary albumin to creatinine ratio, and levels of fasting blood glucose, insulin, serum urea and creatinine, C-reactive protein, serum tumor necrosis factor-α, and serum malondialdehyde (MDA). The polyphenol intervention significantly decreased HbA1c (n = 7 studies; -0.27% [95%CI, -0.51%, -0.04%]), proteinuria (n = 5 studies; -109.10 [95%CI, -216.57, -1.63] mg/24 h), and MDA (n = 5 studies; z-score: -0.41; 95%CI, -0.71, -0.10), and significantly increased GFR (n = 7 studies; 3.65 [95%CI, 0.15-7.15] mL/min/1.73 m2). Overall, studies showed a high risk of bias, and outcomes showed a low or very-low quality in the Grading of Recommendations, Assessment, Development, and Evaluation assessment., Conclusions: There is a clinically modest effect of dietary polyphenols intervention in HbA1c, proteinuria, GFR, MDA, and C-reactive protein levels in patients with DN. It is impossible to establish clinical recommendations, because the evidence was of' low or very-low quality and because of the heterogeneity of types and dose regimens used in the studies., Systematic Review Registration: PROSPERO registration no. ID245406., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)