Objective To study the efficacy of total glucosides of paeony capsule combined with tacrolimus capsule in the treatment of systemic lupus erythematosus (SLE) patients and its regulatory effect on mTOR signaling pathway.Methods The 96 SLE patients admitted to our hospital from January 2016 to January 2019 were selected and divided into control group and observation group according to the random number table method, with 48 cases in each group. Both groups were treated with routine treatment and tacrolimus capsules, while the observation group took total glucosides of paeony capsule on the basis of control group. The therapeutic effects of the two groups were compared, and the levels of peripheral blood immune proteins and molecules associated with the mammalian target of rapamycin (mTOR) signaling pathway before and after the treatment were detected. The incidence of adverse reactions and recurrence rate were also compared between the groups.Results The overall effective rate of the observation group was higher than that of the control group (93.75% VS 79.17%) (P < 0.05). The differences of SLEDAI score and average daily dose of glucocorticoids before and after the treatment were greater in the observation group than those in the control group (P < 0.05). The differences of the levels of peripheral blood immune proteins before and after the treatment in the observation group were higher than those in the control group (P < 0.05). In addition, the differences of the protein levels of the molecules associated with the mTOR signaling pathway (p-Akt, p-PI3K, p-mTOR) before and after the treatment in the observation group were higher than those in the control group (P < 0.05). The major adverse reactions were nausea, fever and diarrhea. There was no difference in the incidence of adverse reactions between the two groups (P > 0.05). The recurrence rate of the observation group was lower than that of the control group (10.86% VS 28.89%) (P < 0.05).Conclusions The total glucosides of paeony capsule combined with tacrolimus capsule is safe and effective in the treatment of SLE patients. It can improve the immune function of patients by inhibiting the mTOR signaling pathway, thereby reducing the recurrence rate and the dose of glucocorticoids.