Four polysaccharides from Dendrobium huoshanense (DHP), D. officinale (DOP), D. nobile (DNP) and D. chrysotoxum (DCP), which had obvious differences in intrinsic viscosities and monosaccharide compositions, were extracted to compare their hypoglycemic and antioxidative activities in alloxan-induced diabetic mice by oral administration. The analysis of fasting blood glucose, glycosylated serum protein and serum insulin levels showed that DHP, DOP and DNP, but not DCP, possessed significant hypoglycemic effect with the decreasing order of DHP>DNP>DOP. Histopathological observation confirmed the capability of DHP, DOP and DNP to intervene the damage in pancreas tissues. The determination of superoxide dismutase, catalase, malonaldehyde and L-glutathione levels in the liver and kidney displayed that DHP, DOP and DNP had protective effects against alloxan-induced oxidative damage and the effect of DHP ranked first. These results suggested that there were significant differences in hypoglycemic and antioxidative activities between four Dendrobium polysaccharides, which may be contributed to their physicochemical properties.