Background/Objectives: Obesity is frequently associated with chronic low-grade inflammation, which contributes to metabolic dysfunction. However, the comparative effects of nutritional supplements on inflammatory biomarkers in adults with overweight or obesity remain unclear. To address this gap, this paper presents a systematic review and network meta-analysis comparing 14 supplementation strategies for their effects on inflammatory biomarkers in this population. Methods: PubMed, Embase, EBSCO, Web of Science, and the Cochrane Library were searched for randomized controlled trials published between January 2000 and January 2026. A frequentist random-effects network meta-analysis was conducted. Effects were reported as mean differences (MDs) with 95% confidence intervals (CIs), and interventions were ranked using the surface under the cumulative ranking curve (SUCRA). The confidence in network estimates was assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. Results: A total of 60 randomized controlled trials were included. Green tea extract (MD = −2.57, 95% CI [−3.99, −1.15]) and curcumin (MD = −1.75, 95% CI [−2.74, −0.76]) both significantly reduced IL-6 levels. Synbiotics (MD = −12.25, 95% CI [−16.7, −7.8]), curcumin (MD = −2.59, 95% CI [−3.83, −1.35]) and probiotics combined with omega-3 (MD = −6.19, 95% CI [−9.12, −3.26]) had a favorable effect on TNF-α. Probiotics combined with omega-3 (MD = −1.74, 95% CI [−3.03, −0.46]), synbiotics (MD = −1.19, 95% CI [−1.85, −0.53]), zinc (MD = −1.18, 95% CI [−2.24, −0.11]), and curcumin (MD = −1.11, 95% CI [−2.14, −0.07]) all reduced CRP levels. Synbiotics (MD = 15.37, 95% CI [12.13, 18.61]) increased adiponectin levels. In contrast, no nutritional supplement significantly reduced leptin levels. Exploratory meta-regression suggested that age, exercise co-interventions, and the proportion of male participants may partly explain heterogeneity in selected outcomes. Conclusions: Nutritional supplements showed biomarker-specific effects. Probiotics combined with omega-3 fatty acids, synbiotics, green tea extract, and curcumin may improve selected inflammatory biomarkers. However, differences in supplement dose, intervention duration, and participant characteristics warrant cautious interpretation and call for further high-quality trials.