This study aimed to investigate whether Jianpi-Zishen Formula (JPZS) modulates the Treg/Th17 balance in MRL/lpr mice through regulation of DNA methyltransferase 1 (DNMT1)-mediated forkhead box P3 (Foxp3) methylation, and to elucidate its potential mechanism for improving immune homeostasis in systemic lupus erythematosus (SLE). Here, DNMT1 is linked to systemic lupus erythematosus.