Conjugated Linoleic Acid (CLA) are thought to pose beneficial effects on inflammatory responses and oxidative stress (OS). Thus, the present systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to assess the net effects of CLA supplementation on various OS parameters and antioxidant enzymes. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched for publications on CLA supplementation effects on OS parameters up to March 2021. The data extracted from eligible studies were expressed as standardized mean difference with 95% confidence intervals and then combined into meta-analysis using the random-effects model. Overall, 11 RCTs (enrolling 586 participants) met the inclusion criteria and were included in meta-analysis; however, since those trials evaluated different OS parameters, meta-analysis was carried out considering different sets for each parameter separately. According to our results, CLA supplementation significantly increases 8-iso-PGF2α urinary concentration (SMD: 2; 95% CI: 0.74, 3.27; I2 = 87.7%). On contrary, the intervention does not seem to change 15-keto-dihydro-PGF2α urinary concentration, nor the serum levels of CAT, SOD, GPx and MDA. Taken all together, CLA supplementation does not appear to have substantial effects on OS markers in general; albeit due to relatively small sample size and high level of heterogeneity between studies, the obtained findings should be interpreted with caution. Further large well-designed RCTs, investigating the impact of CLA and including various groups of patients, are still needed.