Objectives: The purpose of this research was to conduct a meta-analysis of the role that physical activity (PA) plays in influencing the critical proinflammatory cytokine levels associated with overweight/obese children and adolescents to explore the effectiveness of exercise intervention within this population. Methods: With searches of the PubMed, EMBASE, and CENTRAL databases, we updated our meta-analysis up to November 2018. The randomized controlled trials (RCT) evaluated the ability of exercise training to increase the following factors in children and/or adolescents classified as obese or overweight: tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C-reactive protein (CRP). Results: Eleven RCT comprising 623 children and/or adolescents who were obese or overweight (i.e., 393 with PA and 230 controls) were suitable for use in this study. The meta-analysis showed that PA in general was associated with a significant reduction of CRP levels (mean difference = -0.45 mg/L, p = 0.02) in overweight/obese children and adolescents. Based on 115 overweight and obese youths, this study suggests that PA does not significantly mitigate IL-6 levels (mean difference = -0.39 pg/mL, p = 0.08), although there was a trend towards a reduction. Additionally, no close connection was observed between PA and TNF-α levels at 0.04 pg/mL (p = 0.78). Moreover, meta-regression analysis revealed a statistical association between CPR levels and changes in BMI or changes in adiponectin; likewise, IL-6 levels dramatically impacted the effect of exercise on changes in adiponectin. Conclusions: PA was associated with significantly reduced CRP levels, whereas there was no significant association with IL-6 or TNF-α in overweight/obese children or adolescents; however, there was a trend towards a reduction of IL-6.