The invention discloses an efficient and safe chitosan derivative-based disinfection liquid and a preparation method thereof, wherein the components of the formula comprise 0.05-10 g of a chitosan derivative, and 100 ml of sterilized deionized water. According to the present invention, the efficient and safe chitosan derivative-based disinfection liquid has characteristics of exact treatment effect, no toxic-side effect and no irritating to skin, can be used as the sterilization disinfection agent in the medical treatment, can be used for disinfecting skin and mucous membrane, can be used for treating scald, trichomonas vaginitis, fungal vaginitis, skin mold infections, fungal infections and the like, can further be used for burn injury, frostbite, knife wounds, abrasions, contusion and other general trauma, and can be used for pre-surgery disinfection, disinfection of other skins, disinfection of skins in various injection sites, equipment soaking disinfection, disinfection before vaginal surgery, and the like.