The present study aimed to investigate the evidence on the effects of different longterm training interventions (aerobic [AeT], resistance [RT], and combined [COMB]) and spontaneous physical activity (PA) in modifying cytokines and adipokines in individuals with overweight or obesity with or without cardiometabolic diseases while considering potential confounders. Although exercise interventions have become a potentially effective tool for preventing and treating metabolic diseases, the evidence provided by previous systematic reviews is inconclusive since several potential confounders have yet to be addressed. Therefore, we conducted a systematic literature search in Medline, Cochrane, and Embase databases from January 2000 to July 2022 and performed a meta-analysis. Inclusion criteria retrieved 106 full texts comprising 8,642individuals with a range BMI of 25.1-43.8 kg m À2 . We found that independently of the training mode, exercise had a beneficial effect on diminishing Adiponectin, Creactive protein (CRP), IL-6, IL-18, IL-20, Leptin, sICAM, and TNF-α levels circulating levels. Furthermore, by subsequent analysis, we detected differential effects of AeT, RT, and COMB, with sex, age, body composition, and trial length acting as moderators.