Carotid intima-media thickness (c-IMT) is a reliable risk factor for cardiovascular disease risk in type 2 diabetes (T2D) patients. The present study aimed to compare the effectiveness of different machine learning methods and traditional multiple logistic regression in predicting c-IMT using baseline features and to establish the most significant risk factors in a T2D cohort. We followed up with 924 patients with T2D for four years, with 75% of the participants used for model development. Machine learning methods, including classification and regression tree, random forest, eXtreme gradient boosting, and Naïve Bayes classifier, were used to predict c-IMT. The results showed that all machine learning methods, except for classification and regression tree, were not inferior to multiple logistic regression in predicting c-IMT in terms of higher area under receiver operation curve. The most significant risk factors for c-IMT were age, sex, creatinine, body mass index, diastolic blood pressure, and duration of diabetes, sequentially. Conclusively, machine learning methods could improve the prediction of c-IMT in T2D patients compared to conventional logistic regression models. This could have crucial implications for the early identification and management of cardiovascular disease in T2D patients.