BackgroundStroke is the first leading cause of mortality and disability worldwide, and post-stroke spasticity (PSS) is the common complication of stroke. Sangdantongluo Granule, a modern patent Traditional Chinese medicine (TCM), is widely used in clinical practice to treat PSS. Whereas, there is limited evidence of effectiveness for Sangdantongluo Granule to treat PSS. This study will evaluate the clinical efficacy and safety of Sangdantongluo granule in the treatment of PSS. MethodsThis multicenter, randomized, double-blind and placebo-controlled study will recruit 132 participants in China who develops PSS 15 days to 90 days after stroke. Participants will be randomly assigned in an equal ratio to receive either Sangdantongluo granule or placebo for 2 months twice a day orally. The primary measure is the Modified Ashworth Scale (MAS), Secondary outcome measures include Compopsite Spasticity Scale (CSS), Simplified Fugl-Meyer Motor Scale (S-FM), National Institute of Health stroke scale (NIHSS), Modified Rankin Scale (mRS), Modified Barther Index (MBI), and Surface electromyography. Adverse events will be supervised throughout the trial. DiscussionThe results of this study will present whether Sangdantongluo granule is clinical effective and safe for managing PSS.Trial registrationClinicalTrials.gov ChiCTR2100044544. Registered on 23 March 2021.