Purpose <p>A great percentage of deaths globally is attributed to inflammation-related health conditions. Exercise training is proposed as an effective way of reducing chronic systemic inflammation, but the findings of recent studies are inconsistent. The present meta-review of systematic reviews and meta-analyses of interventional studies evaluates the impact of exercise on chronic systemic inflammation.</p> Methods <p>A systematic search of systematic reviews and meta-analyses published in the last 5&#xa0;years (2019–2025) was conducted in MEDLINE and Scopus based on PRISMA Guidelines.</p> Results <p>Of 233 originally retrieved papers, 25 systematic reviews and meta-analyses fulfilled all search criteria and were used for the present meta-analysis which encompassed in total, 30,017 participants. Exercise intervention was associated with significantly reduced mean C-reactive protein (CRP) (pooled mean effect −&#xa0;0.380, 95%CI −&#xa0;0.487, −&#xa0;0.273), Interleukin-6 (IL-6) (pooled mean effect −&#xa0;0.468, 95%CI −&#xa0;0.821, −&#xa0;0.114), and Tumor Necrosis Factor Alpha (TNF-a) levels (pooled mean effect −&#xa0;0.430, 95%CI −&#xa0;0.643, −&#xa0;0.217). Heterogeneity was highly significant (<i>I</i>² was 72.27% for CRP, 96.85% for IL-6 and 90.64% for TNF-a).</p> Conclusions <p>The present findings demonstrated that exercise effectively reduces the levels of biomarkers associated with chronic systemic inflammation. Therefore, public health interventions aimed at physical activity promotion are necessary for chronic systemic inflammation management.</p>