A novel glycopolymer, P(VB-D-ManaH-co-AAm), was prepared by the copolymerization of a new glycomonomer having D-mannaric moieties, VB-D-ManaH, with acrylamide. The resulting glycopolymer and VB-D-ManaH were found to inhibit the β-glucuronidase activity, although D-mannaro-1,4:6,3-dilactone (D-MDL) was known not to do. Additionally, the inhibition ability of P(VB-D-ManaH-co-AAm) was much higher than that of VB-D-ManaH, which was caused by the polymeric cluster effect. Thus, P(VB-D-ManaH-co-AAm) and VB-D-ManaH may be the first D-mannaric strong inhibitors to the β-glucuronidase activity. Lineweaver–Burk plot suggests that the inhibition mechanism of P(VB-D-ManaH-co-AAm) and VB-D-ManaH were not so simple.