To investigate the effectiveness and safety of Jiejing Runmu decoction in relieving the clinical manifestations of dry eye disease (DED). This single-arm prospective intervention study was conducted at the Peking University Third Hospital and People's Hospital of Yongqing. Of the 211 patients recruited, 200 completing the follow-up were included in the analysis. Patients received Jiejing Runmu decoction once a day for 4 weeks continuously, without any change in eye care habits. Individuals were evaluated at four time points: pretreatment (baseline), 2 weeks, 1 month, and 3 months (2 months after completion of treatment), using the Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), corneal fluorescein staining, Schirmer test I and meibomian gland assessments. Adverse effects were evaluated at each follow-up visit and systematic examinations were performed during the first and last visits. OSDI, TBUT, corneal fluorescein staining, Schirmer test I, meibomian gland expressibility, and quality of secretions improved at 2 weeks, 1 month and 3 months compared to baseline (P<0.0001). No significant differences were found between the sexes. Patients above 45 years showed worse subjective symptoms and objective signs, and greater improvements in corneal fluorescein staining, meibomian gland expressibility, and quality of secretions were observed in this group. No obvious adverse effects were detected during any follow-up visit. Jiejing Runmu decoction significantly improved both the subjective symptoms and objective signs of DED, with favorable tolerance.