Sjogren’s syndrome (SS) is characterized by dysfunctional mucous membranes and dysregulated moisture-secreting glands resulting in various symptoms, including dry mouth and dry eyes. Here, we wanted to compare the saliva proteomes of SS mice to healthy controls. Saliva samples were collected and subjected to proteomics workflow to identify alterations in protein levels. We identified differentially expressed genes, including 116 upregulated and 137 downregulated. At same time, dysregulated biological processes mainly focus on cellular, metabolic and immune process.The KEGG analysis showed that complement and coagulation cascades, primarily immunodeficiency, systemic lupus erythematosus, and B cell receptor signaling pathway were riched. We further analyzed DEPs and founded Fn1, klk1b26, HPX and AGT were higher connection scores. These findings improve our mechanistic understanding of the disease and changes in SS mice protein expression will help identify new potential drug targets.