Atherosclerosis is a common cardiovascular disease, the mechanism of which is complex and related to many factors. Changes in the molecular chemical structure of fetoglobulin may play a key role in the development of atherosclerosis. The aim of this study was to reveal how the chemical structure of fetoglobulin affects atherosclerosis and to analyze its association with TyG index and insulin resistance in different sexes. Subjects were patients with confirmed atherosclerosis and were grouped according to carotid color ultrasound and clinical criteria. The chemical structure of fetoglobulin, TyG index, and the role of insulin resistance in atherosclerosis were evaluated by collecting baseline data and conducting corresponding statistical analyses, including multivariate logistic regression analysis. The results showed that the molecular chemical structure of fetoglobulin was significantly different in patients with atherosclerosis. Multivariate logistic regression analysis showed that fetoglobulin level was significantly correlated with the occurrence of carotid atherosclerosis. TyG index and the association between insulin resistance and the incidence of carotid atherosclerosis were also significantly different in different genders.