Polysaccharide decolorization is a key determinant of polysaccharide structure. In this study, two purified Rehmannia glutinosa polysaccharides, RGP−1−A and RGP−2−A, were obtained after decolorization using the AB-8 macroporous resin and H2O2, respectively. RGP−1−A (molecular weight (Mw) = 18,964 Da) and RGP−2−A (Mw = 3305 Da) were acidic and neutral heteropolysaccharides, respectively, and were both polycrystalline in structure. FTIR analysis revealed that RGP−1−A was a sulfate polysaccharide, while RGP−2−A had no sulfate group. Experiments on IPEC-1 cells showed that RGPs alleviated oxidative stress by regulating the Nrf2/Keap1 pathway. These findings were confirmed by the upregulation of Nrf2, NQO1, and HO-1; the subsequent increase in the levels of antioxidant indicators (SOD, LDH, CAT, and MDA); and the restoration of mitochondrial membrane potential. Overall, the antioxidant capacity of RGP−1−A was significantly higher than that of RGP−2−A. These results suggest that RGPs may be a potential natural antioxidant and could be developed into functional foods.