Spinal cord injury (SCI) is a serious nervous system disease. After SCI, a series of cascade reactions will cause irreversible damage, and it has a high disability rate and death rate. The complexity of the pathologic mechanism of SCI limits the efficacy of various traditional therapies, and it is urgent to find new therapeutic means. In recent years, the method of extracting active ingredients from natural Chinese herbs to treat diseases has attracted a lot of attention. Polydatin (PD) is an active ingredient extracted from Polygonum polygonum, and its structure is similar to the traditional drug resveratrol. Sufficient studies have proved that PD plays anti-inflammatory, antioxidant, anti-apoptotic and neuroprotective roles in the treatment of multiple system diseases. These effects are also significant in the treatment of SCI. Based on the structural differences between PD and resveratrol, this paper illustrates the feasibility of using PD in the treatment of SCI, and systematically expounds the pathophysiological process of SCI and the molecular mechanism of PD in the treatment of SCI. In addition, several feasible strategies to improve PD yield and bioavailability are discussed, such as plant protection agent, material loading and drug combination.