The purpose of this systematic review and meta-analysis was to investigate the effects of hesperidin supplementation on inflammatory and oxidative stress biomarkers in human adults. A systematic literature search was conducted in PubMed, EMBASE and Cochrane Central Register of Controlled Trials from inception to 4 January 2025 to identify eligible randomised controlled trials. Ten randomised controlled trials with a total of 532 participants were included. The results indicated that hesperidin supplementation significantly reduced the serum levels of C-reactive protein or high-sensitivity C-reactive protein (SMD: –0·43; 95 % CI –0·71, –0·15; P = 0·002) and TNF-α (SMD: –0·51; 95 % CI –0·95, –0·07; P = 0·02) in adults, while no significant beneficial effect of hesperidin on IL-6 was observed (SMD: –0·25; 95 % CI –0·52, 0·01; P = 0·06). In addition, hesperidin intake showed a beneficial impact on the IL-6 level in patients with diseases (type 2 diabetes and myocardial infarction) (SMD: –0·38; 95 % CI –0·72, –0·04; P = 0·03) yet not in healthy adults without diagnosed diseases. Our findings demonstrated that hesperidin supplementation could lower the serum levels of C-reactive protein or high-sensitivity C-reactive protein and TNF-α in adults.