Chinese herbal medicine is widely cultivated in Southwest China, where the soil cadmium (Cd) contamination of farmland is more serious than that in China as a whole. In this study, Polygonatum sibiricum was exposed to Cd at concentrations of e-1, e0, e2, and e4 mg/kg for 30, 60, and 90 days, and the physiological stress responses, Cd and mineral element uptake, antioxidant enzyme activities, and content changes of pharmaceutical ingredients (polysaccharides) were analyzed to decipher the feasibility of safe utilization in Cd-contaminated soil. The results show that the activity of antioxidant enzymes (SOD and CAT) in the aboveground part was always higher than that in the underground part. The underground part of Polygonatum sibiricum mobilizes nonenzymatic systems to facilitate the synthesis of polysaccharides (PCP1, PCP2) with antioxidant properties to cope with Cd stress. Mineral elements (P, K, Ca, Mg, Fe, Cu, and Zn) significantly (p < 0.05) changed after 90 d of cultivation. In particular, the changes in the iron and zinc content were significantly correlated (p < 0.05) with the activities of SOD and POD. Soil Cd at e0 mg/kg can guarantee the safe production and utilization of Polygonatum sibiricum, and the stimulation of Cd promotes polysaccharide synthesis and biomass growth.