The invention discloses a natural bacteriostatic agent, i.e., an O-quaternary ammonium salt oligochitosan vanillina Schiff base and a preparation method thereof. The preparation method comprises the following steps of: modifying C2-NH2 on the molecular structure of oligochitosan with a strong bacteriostatic action on vanillina to synthesize an oligochitosan vanillina Schiff base; and grafting a quaternary ammonium salt into C6-OH in the structure of the oligochitosan vanillina Schiff base to synthesize the O-quaternary ammonium salt oligochitosan vanillina Schiff base. The preparation method is easy to operate, an operating environment is safe, and the antibacterial property and solubility of an obtained oligochitosan derivative are improved remarkably.