Objective: Several trials investigated the efficacy of L-carnitine administration on markers of inflammation and indicators of oxidative stress; however, their findings are controversial. The aim of this study was to conduct a comprehensive meta-analysis and a critical review, which would analyze all randomized controlled trials (RCTs) in order to determine the effects of L-carnitine supplementation on inflammatory markers and oxidative stress. ----- Methods: An electronic search was performed using Scopus, Cochrane Library, PubMed, Google scholar and Web of Science databases on publications from 1990 up to May 2020. Human RCTs conducted in healthy subjects or participants with certain disorders which investigating the efficacy of L-carnitine supplementation compared to control (placebo, usual treatment or no intervention) on inflammation and oxidative markers were included. Data were pooled applying a random-effects model and as the overall effect size, weighted mean difference (WMD) was presented. Between heterogeneity among studies was computed using Cochran's Q test and I-square (I2). Quality of studies assessed using the Jadad scale. Dose-response analysis was measured using meta-regression. The funnel plot, as well as the Egger's regression test was applied to determine the publication bias. ----- Results: 44 trials (reported 49 effect sizes for different outcomes of interest) met the inclusion criteria for this meta-analysis. According to the findings, L-carnitine supplementation resulted in a significant reduction in C-reactive protein (CRP) (WMD: -0.10; 95% CI: -0.14, -0.06), interleukin 6 (IL-6) (WMD: -1.87; 95% CI: -2.80, -0.95), tumor necrosis factor-α (TNF-α) levels (WMD: -1.43; 95% CI: -2.03, -0.84), and malondialdehyde (MDA) (WMD: -0.47; 95% CI: -0.76, -0.18) levels, while there was a significant increase in superoxide dismutase (SOD) (WMD: 2.14; 95% CI: 1.02, 3.25). However, no significant effects of L-carnitine on glutathione peroxidase (GPx) (WMD: 0.02; 95% CI: -0.01, 0.05) and total antioxidant capacity (TAC) (WMD: 0.14; 95% CI: -0.05, 0.33) were found. ----- Conclusions: L-carnitine supplementation was associated with lowering of CRP, IL-6, TNF-α, and MDA, and increasing SOD levels, but did not affect other inflammatory and oxidative stress biomarkers.