In a previous study, we fractionated crude polysaccharide (AME-CP) with macrophage-stimulating activity from a hot-water extract (AME) of Astragalus membranaceus. AME-CP contained glucose (Glc) as a main component sugar, suggesting that it might be rich in starch-like compounds (SLC). To enhance the immunostimulating activity of AME-CP by pruning SLC rarely known to contribute to activity, hydrolysate (AME-SH) was prepared by digesting with starch-related enzymes, including α-amylase and amyloglucosidase. AME-SH was found to contain substances with molecular weights ranging from 3.9 to 84.4 kDa. These substances were primarily composed of galactose, galacturonic acid, Glc, arabinose, rhamnose, and mannose. AME-SH significantly enhanced the production of macrophage-stimulating factors, including nitric oxide (NO), interleukin (IL)-6, and IL-12, in RAW 264.7 cells compared to AME-CP. Treatment of splenocytes isolated from C3H/HeN mice with AME-SH not only promoted IL-6 secretion, but also induced mitogenic activity. In addition, AME-SH promoted the secretion of hematopoietic growth factors including IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in Peyer's patch (PP) cells and stimulated bone marrow cell proliferation through these PP cells. In conclusion, hydrolysate (AME-SH) digested from AME-CP with starch-related enzymes could be used as a potential immunostimulant.