Obesity is a medical condition influenced by many factors and manifested by the excessive accumulation of fat. It is well documented that oxidative stress plays a significant role in the development of obesity and its related diseases. The antioxidant system's enzymes, such as catalase, superoxide dismutase, glutathione peroxidase, paroxonase, etc., play a significant role in maintaining the oxidant-antioxidant balance in living organisms. Genetic variants of antioxidant system genes may affect the antioxidant system and its efficacy, which can lead to increased oxidative stress and higher risk for the development of obesity and its comorbidities. This review is focused on genetic variants such as single nucleotide polymorphisms of some antioxidant enzymes, ROS generators and transcription factors, and their impact on increased oxidative stress and the development of obesity and medical conditions related to obesity, like insulin resistance and metabolic syndrome.