The aim of our study was to examine the effects of combined physical activity/exercise with diet/nutrition interventions on chronic inflammation indices of healthy overweight and obese children and adolescents. A systematic review and meta-analysis (registration number: INPLASY2024110126), following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and the Cochrane handbook, was conducted. We searched PubMed, Ovid, SportDiscus, and Web of Science up to February 2025. Fifty publications that met the eligibility criteria were included. The results showed that C-reactive protein (CRP) was decreased due to intervention (Standardized mean difference (SMD) -0.53; 95% confidence interval (CI) -0.78 to -0.28). Interleukin (IL)-6 was reduced due to intervention (SMD -0.53; CI -0.83 to -0.22), while meta-analysis for tumour necrosis factor alpha (TNF-alpha) showed no effect (p > 0.05). Also, IL-8 was reduced due to intervention (SMD -0.37; CI -0.61 to -0.13), while no changes in IL-10 were found (p > 0.05). Meta-analysis for IL-1beta showed a significant decrease due to intervention (SMD -0.51; CI -0.94 to -0.08). Final interpretation of the results, which is based on the certainty of evidence and the magnitude of effect, led to the conclusions that combined physical activity/exercise with diet/nutrition interventions likely reduces CRP, IL-6, and IL-1beta, while probably reduces IL-8 in healthy overweight and obese children and adolescents.

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