Introduction: The purpose of the present study was to appraise the results from disseminated human, animal and in vitro studies, and evaluate the possible effect along with the mechanism of CLA supplementation on endurance exercise. Methods: Related articles were searched on PubMed, Web of Science, Scopus, Embase, and Cochrane databases with defined keywords. Articles were assessed through their titles and abstracts. Finally, 11 articles were included based on inclusion and exclusion criteria. Results: Most of the studies were conducted on animals, and CLA was often supplemented along with training. Dosage and study duration vary for a broad range. Results showed various possible pathways on the effect of CLA supplementation on endurance exercise and related factors. Conclusions: It was indicated that CLA supplementation could prolong endurance performance by improving oxidant status, mitochondrial biogenesis, testosterone biosynthesize, fat oxidation, and change in body composition. Although CLA is being used in many countries and numerous studies have shown its safety, its long-term supplementation and effect need to be investigated. Also, further studies are required to identify the molecular mechanism in the human body.