Background and Objectives: Atherosclerosis is a chronic inflammatory disease significantly contributing to cardiovascular morbidity and mortality. This study primarily aims to evaluate the role of baseline blood glucose levels and inflammatory markers in the histopathological features of atherosclerotic plaques in the carotid and femoro-popliteal arteries. Materials and Methods: In this retrospective, observational, and monocentric study, 165 patients diagnosed with infrainguinal peripheral arterial disease or carotid artery disease hospitalized in the Vascular Surgery Clinic, between January 2019 and December 2023, were included. From the electronic database of the hospital, we documented demographic data, cardiovascular comorbidities, including hypertension, atrial fibrillation, ischemic heart disease, and chronic heart failure, as well as chronic kidney disease, diabetes, and prevalent risk factors such as active smoking, dyslipidemia, and obesity. Additionally, we recorded the arterial site from which the atherosclerotic plaque was obtained, along with laboratory data obtained at the time of admission prior to the surgery. The patients were divided into "Carotid Artery" and "Femoro-Popliteal Axis" based on anatomical location. Results: A greater prevalence of male patients (p = 0.008) and dyslipidemia (p = 0.002) was found in the group with atherosclerotic plaques from the femoro-popliteal axis. Laboratory data also showed increased lymphocyte (p = 0.020) and PLT (p = 0.028) levels in this group. There was no significant difference in the types of atherosclerotic plaques between the two patient groups. However, those in the Carotid Artery group showed a higher rate of antiaggregant treatment and a reduced incidence of dual therapy (p < 0.001). The Spearman correlation analysis revealed a positive correlation between baseline glucose levels and NLR (r = 0.402, p < 0.001), MLR (r = 0.217, p = 0.005), PLR (r = 0.306, p < 0.001), and LGI (r = 0.693, p < 0.001). Furthermore, the predictive roles of glucose, NLR, MLR, and LGI were assessed through multivariate analysis. Consequently, elevated baseline values of the parameters above were associated with unstable atherosclerotic plaques, independent of demo-graphic data, standard cardiovascular risk factors, site of artery harvest, and chronic vascular treatments at the time of admission (for all p < 0.05). Conclusions: This study highlights the significant relationships between glucose levels and various inflammatory markers in patients with different histopathological diagnoses of atherosclerotic plaques. Additionally, elevated glycemic and systemic inflammation biomarkers were associated with unstable atherosclerotic plaque, independent of demographic data, comorbidities, cardiovascular risk factors, anatomical artery harvest, and vascular chronic medication at the time of admission.