In this paper, three purified Mori Fructus (M. Fructus) polysaccharides (MFP-1, MFP-2 and MFP-3) were successfully obtained from M. Fructus. Structural modification methods, including oxidative degradated, sulfated and carboxymethylated modification, were conducted and nine MFPs derivatives were obtained. The molecular structures of MFPs were studied and the results showed that MFP-1, MFP-2 and MFP-3, mainly composed of Ara, Gal, Rha, Glc and GalA, with a molecular weight approximately of 20.93 kDa, 56.23 kDa and 118.76 kDa, respectively. FT-IR spectrum of these MFPs all revealed the characteristic polysaccharide absorption bands, while the MFPs derivatives also exhibited some differences due to the structure modification. Hepatoprotective activities tests showed that MFP derivatives could significantly improve the alcohol dehydrogenase (ADH) activity by comparing with the native MFP. And among them, the C-MFP exhibited higher protection effect than the other two modification derivatives.