Intrinsically disordered regions (IDRs) are central to liquid–liquid phase separation (LLPS), yet how post-translational modifications (PTMs) selectively regulate IDR-driven phase behavior remains unclear. Here, we systematically analyze PTMs across RNA-binding proteins (RBPs), a protein class highly enriched in IDRs. By integrating curated PTM databases with quantitative chemoenzymatic profiling, we find that although many RBPs are O-GlcNAc modified, only a small fraction (~5%) exhibits high-level O-GlcNAcylation. Notably, all highly modified RBPs undergo LLPS but display diverse condensate dynamics, indicating context-dependent regulation. Mechanistic analyses of representative candidates reveal that O-GlcNAcylation can exert opposing effects on LLPS depending on protein context.