Abstract: Recent breakthroughs in antibody modification technologies have propelled the rapid development of antibody-drug conjugate(ADC) for cancer treatment. Compared to traditional site-specific conjugation techniques, achieving precise site modifications on natural antibodies offers significant advantages, such as eliminating the need for antibody engineering and simplifying the conjugation process. This article provides a comprehensive overview of the cutting-edge advancements in site-specific conjugation technologies targeting natural antibodies, categorized into six major types: adjacent modification, glycan remodeling, interchain disulfide bridging, enzymatic conjugation, chemical modification, and DNA-mediated site-specific conjugation. It also analyzes various emerging ADC conjugation technologies, including AJICAP and DTPC, with the aim of providing new insights for the development of the next generation of antibody conjugation technologies.