Protein glycation inhibitors from Polygonatum odoratum rhizomes were investigated using a bioassay-guided procedure to characterize active compounds for preventing and treating diabetic complications. The EtOH extract and soluble fractions were evaluated using an in vivo model of renal advanced glycation end-product (AGE) accumulation in streptozotocin-induced diabetic rats and an in vitro bovine serum albumin-glucose assay. Three homoisoflavanones 3-(4'-hydroxybenzyl)-5,7-dihydroxy-6-methyl-8-methoxychroman-4-one (1), 3-(4'-hydroxybenzyl)-5,7-dihydroxy-6,8-dimethylchroman-4-one (2), and 3-(4'-methoxybenzyl)-5,7-dihydroxy-6-methyl-8-methoxychroman-4-one (3), isolated from the active CHCl3-soluble fraction of the EtOH extract, were subjected to in vitro bioassays to evaluate their inhibitory activities against AGE formation. All the isolates inhibited AGE formation more effectively than the positive control, aminoguanidine. These results indicate that pending further study these compounds could be used as novel natural product drug for mitigating diabetic complications.