Introduction: The correct interaction between elements of the endocannabinoid system plays an important role in the development of the central nervous system. Clinical and preclinical studies suggest that cannabidiol (CBD) may be useful for athletes due to its anti-inflammatory, analgesic, anxiolytic, and neuroprotective properties and its influence on the sleep-wake cycle. In addition, a series of implications for epigenetic processes have also been proven, through changes in the expression of microRNAs responsible for modulating the immune and inflammatory systems. Objective: It was to develop a systematic review study to highlight the main aspects of cannabidiol in the interaction with microRNAs and exosomes in the modulation of inflammatory and immunological processes in athletes. Methods: The systematic review rules of the PRISMA Platform were followed. The research was carried out from February to April 2023 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 228 articles were found, and 84 articles were evaluated in full and 33 were included and developed in this systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 20 studies with a high risk of bias and 90 studies that did not meet GRADE. CBD has been reported to exert a range of physiological, biochemical, and psychological effects with the potential to benefit human health. For example, there is preliminary supporting evidence for the anti-inflammatory, neuroprotective, analgesic, and anxiolytic actions of CBD and the possibility that it may protect against gastrointestinal damage associated with inflammation and promote the healing of traumatic skeletal injuries. The combination of Δ9-THC and CBD can alter the activity of microRNAs responsible for increasing the biosynthesis of inflammatory mediators, leading to a reduction in the inflammatory profile. However, it is important to recognize that these findings are very preliminary, sometimes inconsistent, and largely derived from preclinical studies. These studies are limited in their generalizability to athletes and often administer high doses of CBD. The central observation is that there is a lack of studies that directly investigate CBD and sports performance.