IntroductionObesity is a disorder characterized by a disproportionate increase in body weight in relation to height, mainly due to the accumulation of fat, and is considered a pandemic of the present century by many international health institutions. It is associated with several non-communicable chronic diseases, namely, metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and cancer. Metabolomics is a useful tool to evaluate changes in metabolites due to being overweight and obesity at the body fluid and cellular levels and to ascertain metabolic changes in metabolically unhealthy overweight and obese individuals (MUHO) compared to metabolically healthy individuals (MHO).ObjectivesWe aimed to conduct a systematic review (SR) of human studies focused on identifying metabolomic signatures in obese individuals and obesity-related metabolic alterations, such as inflammation or oxidative stress.MethodsWe reviewed the literature to identify studies investigating the metabolomics profile of human obesity and that were published up to May 7th, 2019 in SCOPUS and PubMed through an SR. The quality of reporting was evaluated using an adapted of QUADOMICS.ResultsThirty-three articles were included and classified according to four types of approaches. (i) studying the metabolic signature of obesity, (ii) studying the differential responses of obese and non-obese subjects to dietary challenges (iii) studies that used metabolomics to predict weight loss and aimed to assess the effects of weight loss interventions on the metabolomics profiles of overweight or obese human subjects (iv) articles that studied the effects of specific dietary patterns or dietary compounds on obesity-related metabolic alterations in humans.ConclusionThe present SR provides state-of-the-art information about the use of metabolomics as an approach to understanding the dynamics of metabolic processes involved in human obesity and emphasizes metabolic signatures related to obesity phenotypes.