Although inflammation and oxidative stress have been increasingly recognised as components of Alzheimer's disease (AD) and Parkinson's disease (PD) pathologies. Few studies have investigated peripheral inflammation, and none have examined oxidative stress in Dementia with Lewy bodies (DLB). The purpose of our study was to characterize and compare those biomarkers in DLB with those in AD and amnestic mild cognitive impairment (aMCI). Plasma samples were obtained from Chinese patients with DLB (n = 50), AD (n = 59), and aMCI (n = 30), and healthy controls (HCs) (n = 54). Peripheral inflammatory biomarkers, including interferon-gamma (IFN-γ), interleukins (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Oxidative stress markers, such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px), were also assessed. The findings revealed that DLB patients had higher IL-6 levels than AD and HCs and elevated IL-10 and IL-17A levels compared to HCs. In terms of oxidative stress, the levels of SOD were significantly lower and MDA were significantly higher in the DLB and AD compared with HCs. Significant positive correlations were found between Unified Parkinson's Disease Rating Scale (UPDRS) scores and CRP levels. Our study identifies a unique peripheral immune and oxidative stress profile in DLB, characterized by elevated IL-6, MDA, and reduced SOD levels, distinguishing it from AD. These findings, linked to α-synuclein (α-Syn) pathology, provide novel insights into DLB mechanisms and highlight potential biomarkers for disease monitoring, targeted therapies, and future clinical trials.Copyright © 2025 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.