Aim and design: L-carnitine supplementation combined with exercise may enhance metabolic responses and improve exercise performance. Thus, this systematic review article aims to identify the effects of the L-carnitine supplement on biochemical markers, and exercise performance when combined with exercise. Data Sources: The articles are screened and reviewed based on titles, abstracts and keywords. Only peer-reviewed studies written in the English language, dated January 2000 to March 2021, were considered in this review. Review Methods: The PRISMA method is used for this study. PubMed, EBSCOHost, SpringerLINK, and Scopus databases were used to systematically search. Results: From a search 731 articles, 12 articles were identified related to effect of L-carnitine intake with exercises on biochemical markers and exercise performance. Studies showed that L-carnitine supplementation can be consumed daily during aerobic or anaerobic exercises by different population including patients. Its combination could improve serum lipid profiles, antioxidant properties, markers of metabolic, oxidative stress, and inflammatory, and exercise performance. Conclusion and Impact: This review provides information regarding the beneficial effects of L-carnitine supplement with recommended dosages and exercise prescriptions on overall body health in human.