Objective: To assess the effectiveness and safety of the total glucosides of paeony (TGP) combined with Hydroxychloroquine (HCQ) on the treatment of primary Sjögren’s syndrome (pSS) by conducting a meta-analysis. Methods: Eight databases were searched for randomized controlled trials reporting the use of TGP combined with HCQ for pSS, which are before May 10,2022. Meta analyses were performed on disappeared clinical symptoms (dry mouth, dry eyes),schirmer’s test, saliva flow test, erythrocyte sedimentation rate (ESR), index of immunoglobulin G(IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), and adverse events (AEs). The Revman 5.4 software was used for this Meta-analysis.Results: Seven RCTs which included 632 participants were identified.The pooled results showed significant differences in clinical symptoms disappear(dry mouth, dry eyes)(P=0.0004), IgM(P < 0.00001) , IgA(P < 0.00001) , salivary flow rate(P < 0.00001) and schirmer’s test(p=0.02) in the comparison of TGP combined with HCQ and HCQ alone. For the IgG and ESR, both pooled and subgroup analyses showed that TGP+HCQ was superior to HCQ alone. For the safety analysis, no significant differences in AEs(P=0.39) was revealed. The more frequently seen adverse reactions were diarrhea, vomit and there was no severe adverse events were reported in TGP+HCQ group. Conclusion: Therefore, TGP+HCQ can be considered to be a potentially valid and safe combination for the treatment of pSS in the clinic.