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The objectives of the present study are to synthesize a series of chitosan oligosaccharide-O-Terpenol (COS-O-Ter) derivatives and their implication to evaluate in vitro antibacterial activity. Herein, a general strategy is described for preparing COS-O-Ter derivatives, including substitution and deprotection reactions. The structures of COS-O-Ter derivatives were characterized by FT-IR, 1H NMR, XRD, TGA, and elemental analysis. COS-O-Ter derivatives revealed the excellent solubility and in vitro antibacterial activity. Moreover, their