INTRODUCTION: Primary Sjogren's Syndrome (pSS) is a chronic inflammatory autoimmune disease that manifests as dry mouth and eyes. Luteolin can repress immuno-inflammation and improve the function of exocrine glands. METHODS: Bibliometrics was used to visualize pSS-related key indicators. The efficacy of traditional Chinese medicines (TCMs) in pSS treatment was analyzed with the internal database containing the clinical records of pSS. Using the network pharmacology technology to identify involved pathways. Additionally, molecular docking and cell experiments were performed to screen and verify the therapeutic effect of luteolin on pSS. RESULTS: Key indicators that were selected according to the bibliometrics were worse in pSS and had certain compatibility and correlation with laboratory and immunoinflammatory indicators. After treatment, pSS patients showed improvements in the above indicators. The results of risk analyses revealed that TCMs were protective factors for laboratory indicators and key indicators. The main effective TCMs for pSS treatment and TNF pathways were identified with network pharmacology. Cell experiments validated that luteolin indeed improved the secretion dysfunction and inflammation of modeled human submandibular gland epithelial cells through the TNF/NF-κB pathway. CONCLUSIONS: TCMs may effectively improve transcription factors and immuno-inflammatory markers in pSS patients. Moreover, we hypothesized and verified the potential mechanism of action of luteolin in HSG cells.