Studies investigating the effects of spirulina on inflammation and oxidative stress status are controversial. Therefore, the current systematic review and meta-analysis aimed to evaluate the impacts of spirulina supplementation on oxidative stress indicators and inflammatory markers. PubMed-Medline, SCOPUS, Web of Science, Embase databases and Google Scholar were searched up to 1 October 2020. Random-effect analysis was applied to perform meta-analysis. Subgroup analyses and multivariate meta-regression were performed to find heterogeneity sources. Quality assessment was conducted using Cochrane Collaboration's tool. A total of 11 studies that enrolled 465 subjects were included in our meta-analysis. Pooled results demonstrated a significant increase in interleukin-2 (IL-2) concentrations [Standardized mean difference (SMD = 2.69 pg/mL; 95% CI: 0.26, 5.11; P = .03)]; however this result changed to insignificant (SMD = 0.54 pg/mL; 95% CI: -1.29, 2.27; P > .05) when sensitivity analysis performed. A marginal decreasing effect were also found on interleukin-6 (IL-6) (SMD = -0.72 mg/dL; 95% CI: -1.50, 0.07; P = .073) and thiobarbituric acid reactive substances (TBARS) levels (SMD = -0.65; 95% CI: -1.37, 0.08; P = .08). In addition, results of subgroup analysis revealed a significant reduction in IL-6 and TBARS concentrations when the baseline body mass index (BMI) of participants was lower than 25 kg/m . Moreover, spirulina had no significant effect on tumour necrosis factor-α (TNF-α) (SMD = -0.07 mg/dL; 95% CI: -0.33, 0.18; P = .56) and malondialdehyde (MDA) concentrations (SMD = -0.42; 95% CI: -0.98, 0.14; P = .14). Spirulina consumption contributed to a significant increase in IL-2 concentrations changing to insignificant after sensitivity analysis and marginal decreasing effects on IL-6 and TBARS levels. No considerable impacts were observed on TNF-α and MDA concentrations.