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The present application belongs to the technical field of natural product chemical modification, and particularly relates to a chemically modified rare ginsenoside derivative, a preparation method and application thereof. The present application takes rare ginsenoside as raw material, introduces a sulfate group by sulfating modification on the rare ginsenoside to obtain a chemically modified rare ginsenoside derivative; the modifier used in the sulfating modification is a sulfonating agent. The rare ginsenoside is synthesized by conversion with ginsenoside Rb1 as raw material and AlCl3 as catalyst in an ethanol system. The modification method of the present application is simple in operation steps, does not require special equipment, is suitable for large-scale production, and has a broad application prospect in the field of drug preparation development and the like.