Effective monitoring of glucose levels is necessary for patients to achieve greater control over their diabetes. However, only about a quarter of subjects with diabetes who requires close serum glucose monitoring, regularly check their serum glucose daily. One of the potential barriers to patient compliance is the blood sampling requirement. Saliva and its protein contents can be altered in subjects with diabetes, possibly due to changes in glycemic control. We propose here that salivary proteomes of subjects with diabetes may be different based on their glycemic control as reflected in A1C levels. A total of 153 subjects with type 1 or 2 diabetes were recruited. Subjects in each type of diabetes were divided into 5 groups based on their A1C levels; <7, 7–8, 8–9, 9–10, >10. To examine the global proteomic changes associated with A1C, the proteomic profiling of pooled saliva samples from each group was created using label-free quantitative proteomics. Similar proteomic analysis for individual subjects (N=4, for each group) were then applied to examine proteins that may be less abundant in pooled samples. Principle component analysis (PCA) and cluster analysis (p<0.01 and p<0.001) were used to define the proteomic differences. We, therefore, defined the salivary proteomic changes associated with A1C changes. This study demonstrates that differences exist between salivary proteomic profiles in subjects with diabetes based on the A1C levels.