Levodopa preparations remain the preferred drug for Parkinson's disease. However, long-term use of levodopa may lead to a series of motor complications. Previous studies have shown that the combination of levodopa and Zishenpingchan granules (consisting of Radix Rehmanniae preparata, Lycium barbarum, Herba Taxilli, Rhizoma Gastrodiae, Stiff Silkorm, Curcuma phaeocaulis, Radix Paeoniae Alba, Rhizoma Arisaematis, Scorpio and Centipede) can markedly improve dyskinesia and delay the progression of Parkinson's disease, with especially dramatic improvements of non-motor symptoms. However, the efficacy of this combination has not been confirmed by randomized controlled trials. The current study was approved by the Hospital Ethics Committee and was registered in the Chinese Clinical Trial Register (registration number: ChiCTR-INR-1701194). From December 2014 to December 2016, 128 patients (72 males and 56 females, mean age of 65.78 ± 6.34 years) with Parkinson's disease were recruited from the Department of Neurology of Longhua Hospital and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine in China. Patients were equally allocated into treatment and control groups. In addition to treatment with dopamine, patients in treatment and control groups were given Zishenpingchan granules or placebo, respectively, for 24 weeks. Therapeutic efficacy was assessed using the Unified Parkinson's Disease Rating Scale, on-off phenomenon, Hoehn-Yahr grade, Scales for Outcomes in Parkinson's disease-Autonomic, Parkinson's disease sleep scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Mini-Mental State Examination, and the Parkinson's Disease Quality of Life Questionnaire. Artificial neural networks were used to determine weights at which to scale these parameters. Our results demonstrated that Zishenpingchan granules significantly reduced the occurrence of motor complications, and were useful for mitigating dyskinesia and non-motor symptoms of Parkinson's disease. This combination of Chinese and Western medicine has the potential to reduce levodopa dosages, and no obvious side effects were found. These findings indicate that Zishenpingchan granules can mitigate symptoms of Parkinson's disease, reduce toxic side effects of dopaminergic agents, and exert synergistic and detoxifying effects.