Introduction: Obesity represents a pandemic represented as a chronic, long-term imbalance between calorie intake and energy expenditure. MicroRNAs (miRNAs) stand out. They are a class of small non-coding RNAs that regulate gene expression, and changes in their expression and functions have been associated with many diseases, including metabolic disorders and obesity. Objective: It was to present the main considerations and results of clinical studies on the relationship between obesity, gut microbiota, and microRNAs in inflammatory and immunological processes through a systematic review. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from August to September 2023 in the Web of Science, 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 121 articles were found, and 44 articles were evaluated in full and 30 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 22 studies with a high risk of bias and 21 studies that did not meet GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2=77.5%>50%. It was concluded that microRNAs regulate gene expression in adipose tissue, impact the regulation of metabolism and energy homeostasis, and regulate adipogenesis signaling pathways in white, beige, and brown adipose tissue. For example, microRNA (miR-143) promotes brown adipose tissue thermogenesis and inhibits white adipose tissue adipogenesis. Some miRNAs have been implicated in the control of body weight gain, glucose homeostasis, insulin resistance, and lipid metabolism, with crosstalk with the gut microbiota. Furthermore, an association was found between B. eggerthi abundance, miR-183-5p expression, and adiponectin levels. Expression of miR-15a-5p was found to be associated with H. parainfluenzae abundance and insulin levels.