Knee osteoarthritis (KOA) is a prevalent chronic condition characterized by inflammation and oxidative stress, particularly in individuals over 40. Dietary factors, specifically dietary acid load (DAL), may influence these pathological processes. However, the relationship between DAL and inflammatory markers, oxidative stress, and clinical features in patients with KOA remains unexplored. This cross-sectional study involved 147 participants aged 40 and above diagnosed with moderate to severe bilateral primary KOA. Dietary intake was assessed using a validated food frequency questionnaire, and DAL was quantified using Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) indices. Clinical symptoms were evaluated using the WOMAC Index. Biochemical markers of oxidative stress and inflammation were measured from serum samples. Higher PRAL and NEAP scores were associated with increased levels of thiobarbituric acid reactive substances (TBARS) and total oxidant status (TOS), indicating elevated oxidative stress. Additionally, serum levels of inflammatory markers, including TNF-α and hs-CRP, positively correlated with higher DAL scores. Clinical assessments revealed that increased PRAL scores were related to greater severity of symptoms as measured by the WOMAC Index. This study demonstrates a significant association between dietary acid load and markers of inflammation and oxidative stress in KOA patients. These findings suggest that dietary modifications aimed at reducing acid load may serve as a beneficial adjunctive strategy in managing KOA and improving patient outcomes.© 2025. The Author(s).