Glycosite-specific antibody-drug conjugates (gsADCs), which carry cytotoxic payloads at the conserved N-glycosylation site, N297, of an IgG, have emerged as a promising ADC format with better therapeutic index. Conjugating the payloads via aldehyde-based chemistry is more friendly to IgGs, and has been widely investigated. However, the efficiency of introducing an aldehyde tag at the N297 site is poor due to the complicated procedures required, such as the multiple-enzyme-catalyzed IgG glycoengineering process and the successive oxidation step, which always results in heterogeneous products and poor stability. Herein, we report an efficient approach to assemble aldehyde-based gsADCs, in which the aldehyde group is first protected by hydrazine and conjugates linker-payloads via an acylhydrazone-oxime exchange reaction. This method exhibits remarkable coupling efficiency to various linker-payloads, and the corresponding gsADCs demonstrate good homogeneity, stability, and in vitro and in vivo efficacy.