The invention discloses site-specific mono-PEGylated Exendin analogs in which any amino groups can be mono-PEGylated as well as their preparation method and use. The method of the present invention adopts a more stable protective group Dde (N-α-1-(4,4-dimethyl-2,6-dioxo-cyclohexylene)) to avoid multi-PEGylated side reactions rendered by unstable protecting groups, achieving mono-PEGylated Exendin analogs at a high recovery with a low reaction molar ratio.
