Objective：The efficacy of total glucosides of paeony（TGP）in the treatment of Sjögren’s syndrome（SS）and its relationship with inhibition of nucleotide binding oligomerization domain（NOD）-like receptor pyrin domain containing 3（NLRP3） inflammasome activation were investigated，so as to clarify the novel mechanisms of TGP on treatment of SS. Methods：Female non-obese diabetic mice were selected as the model of SS. The non-obese diabetic mice were intragastric administrated with TGP（400 mg/kg）for 1 month. The saliva flow rates of mice were measured. The lymphocyte infiltration in submandibular gland was determined. The NLRP3 inflammasome activation of spleen was detected. In vitro，the NLRP3 inflammasome was activated in cultured splenocytes with 100 μg/mL TGP treatment. Then，the NLRP3 inflammasome activation was determined by RT -qPCR and Western blot. Results：Compared with the mice of control group，the saliva flow rates were significantly increased（P＜0.05）and the lymphocyte infiltration in submandibular gland was significantly reduced in non-obese diabetic mice of TGP treatment group. The NLRP3 inflammasome of spleen was inhibited in non-obese diabetic mice with TGP treatment（P＜0.05）. In vitro，the NLRP3 inflammasome activation of splenocytes was also suppressed by TGP（P＜0.05）. Conclusion：TGP alleviates SS-like symptoms in non-obese diabetic mice，and these beneficial effects are related to the inhibition of NLRP3 inflammasome activation. These findings not only uncover the novel mechanisms of therapeutic effects of TGP in SS，but also provide new evidences for application of TGP in treatment of SS patients.