Peptides　and　proteins　undergo　crucial　modifications　to　alter　their　physicochemical　properties　to　expand　their　applications　in　diverse　fields.　Various　techniques,　such　as　unnatural　amino　acid　incorporation,　enzyme　catalysis,　and　chemoselective　methods,　have　been　employed　for　site-selective　peptide　and　protein　modification.　While　traditional　methods　remain　valuable,　advancement　in　host-guest　chemistry　introduces　innovative　and　promising　approaches　for　the　selective　modification　of　peptides　and　proteins.　Macrocycles　exhibit　robust　binding　affinities,　particularly　with　natural　amino　acids,　which　facilitates　their　use　in　selectively　binding　to　specific　sequences.　This　distinctive　property　endows　macrocycles　with　the　potential　for　modification　of　target　peptides　and　proteins.　This　review　provides　a　comprehensive　overview　of　strategies　utilizing　macrocycles　for　the　selective　modification　of　peptides　and　proteins.　These　strategies　unlock　new　possibilities　for　constructing　antibody-drug　conjugates　and　stabilizing　volatile　medications.　©　2024　American　Chemical　Society