Systemic lupus erythematosus (SLE) is an autoimmune disease that affects various organs in the body. In SLE, inflammatory cytokines play a crucial role in initiating and sustaining the inflammatory process. Synbiotics may help modulate these inflammatory cytokines. This randomized, double‐blind, placebo‐controlled clinical trial aimed to assess the impact of synbiotics intervention on interleukin‐17A (IL‐17A) levels, disease activity, and inflammatory factors in patients with SLE. Fifty SLE patients were randomly assigned to receive either standard therapy plus synbiotics (consisting of Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus salivarius, Lactobacillus reuteri, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium bifidum, and the prebiotic fructooligosaccharides) or standard therapy alone for 2 months. The results demonstrated a significant reduction in both protein and mRNA levels of IL‐17A, as well as in the Systemic Lupus Erythematosus Disease Activity Index 2000 score, within the synbiotics group after the intervention compared to baseline. In contrast, the placebo group did not experience significant changes in IL‐17A levels or disease activity. Synbiotic supplementation shows potential as an adjunctive therapeutic approach for SLE management; however, further research is needed to elucidate its underlying mechanisms.Practical ApplicationThis study explores the use of synbiotics as a supplementary treatment for systemic lupus erythematosus, which is typically managed with immunosuppressive therapies.