The effect between biocompatible low molecular weight chitosan derivatives as the delivery carrier of active pharmaceuticals bovine serum album (BSA) was studied. Three derivatives of low molecular weight chitosan with 20 degree of polymerization (NLCS20) and narrow molecular weight distribution including N-maleoyl-NLCS20, N-carboxymethyl-NLCS20 and N-succinyl-NLCS20 were synthesized. The effect between NLCS20 derivatives and BSA was studied with UV spectrum, fluorescence spectrum and isothermal titration calorimetry (ITC). The results showed that the conformation and activity of BSA did not change a lot in the microenvironment of NLCS20 derivatives solution. The process was exothermic and spontaneous. The main binding force was hydrogen bond and hydrophobic interaction. It was concluded that low molecular weight derivatives are likely to be delivery carriers of hydrophilic drugs such as active protein or poly amino acid.