Due to being correlated with metabolic syndrome, diabetes mellitus, cardiovascular disease, fatty liver disease, and cancer, obesity is a global health issue that predisposes to morbidity and mortality. Obesity can be defined as an excessive amount of fat accretion in the body. According to current research, visceral adipose tissue performs a critical function as an active endocrine organ due to its function in releasing adipokines that facilitate complex physiological events. These adipokines exacerbate both low-grade inflammation and oxidative stress (OS), two key constituents of obesity-related comorbidities. This review summarizes the most recent data on the relationship between inflammation, OS, and diseases linked to obesity, focusing on how OS overexpression causes cellular damage by weakening antioxidant mechanisms. To understand the mechanisms by which OS is related to comorbidities, we assess a wide range of models, including animal models, biochemical analysis, and clinical research. The most important discoveries are that heightened OS exacerbates inflammation and cellular damage by increasing the formation of ROS and weakening antioxidant defenses. Increased lipid peroxidation and oxidative damage in adipose tissue associated with insulin resistance and metabolic dysfunction have been identified through data from research conducted on KKAy mice, a model of diabetes obesity. Adipokines, like adiponectin, have been shown to have protective functions against inflammation and OS. Thereby, some of these candidates may become promising therapeutic targets. Understanding the mechanism of these systems is a must for developing such therapies to decrease OS, redress antioxidant imbalance, and reprogram inflammatory pathways. Such tactics may further augment clinical outcomes and reduce the occurrence of obesity-associated diseases in global populations.