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The main components of PMP mucus are highly O\u2010glycosylated proteins called mucins. Represented by mucin2 (MUC2), mucins are the source of mucus viscoelasticity. This review investigated detailed processes of mucin O\u2010glycosylation and mucolytic therapies in PMP. We introduced molecular pathological mechanism of PMP, types of mucus and mucins in PMP, molecular structure and biological functions of mucins. We focus on the synthesis process and physiological functions of MUC2 O\u2010glycosylation. Furthermore, we summarize the potential therapeutic approaches to inhibiting mucin secretion and mucolysis. Detailed process of mucin O\u2010glycosylation in endoplasmic reticulum and Golgi apparatus was discussed. We discussed promising approaches to targeting the substrates and enzymes in O\u2010glycosylation, including uridine diphosphate and GalNAc analogs\/derivatives, ppGalNAc\u2010T\/GALNT inhibitors, disulfide bond reducing agents or PDI inhibitors, O\u2010glycosidases, and glucoproteinases. 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