Tocotrienols, isomers of vitamin E, may provide an effective nutritional strategy to mitigate common cardiovascular risks such as dyslipidemia, inflammation, and oxidative stress in patients with chronic kidney disease (CKD). This double-blind, placebo-controlled, randomized clinical trial aimed to evaluate the effects of a tocotrienol-rich fraction (TRF) supplementation (300 mg/day) on oxidative stress and inflammatory markers, including transcription factors in nondialysis (ND) and hemodialysis (HD) CKD patients for three months. Interleukin-6, tumor necrosis factor- (IL-6 and TNF-), C-reactive protein (CRP), lipid peroxidation, biochemical parameters, and transcription factors such as NRF2 and NF-B mRNA expression were evaluated. Seventeen HD patients (9 in the placebo group, 8 in the TRF group) and 16 ND CKD patients (8 in the placebo group and 8 in the TRF group) completed the study. In HD patients, significant reductions were observed in LDL cholesterol (=0.04) and total plasma cholesterol levels (=0.01) after TRF intervention. CRP serum levels decreased significantly in ND CKD patients (=0.05) after TRF supplementation. Transcription factors NRF2 and NF-B mRNA expressions remained unaltered in both groups. This study suggests that TRF supplementation may mitigate dyslipidemia and inflammation, factors involved with increased cardiovascular risk, in CKD patients, with variations in efficacy between HD and ND patients. ClinicalTrials.gov identifier: NCT04900532.