Phenytoin sodium is widely used to cure antiepileptic, trigeminal neuralgia, sciatica, paroxysmal choreoathetosis, myotonia, arrhythmia, hypertension and so, but a common and well-known adverse effect of its administration is gingival over -growth which may influence the aesthetics and oral function. The pathogenesis of Phenytoin sodium-induced gingival over-growth is not very clear now. This review summarized the mechanism of Phenytoin sodium-induced gingival over-growth, fibroblast cell proliferation and programmed cell death, collagen homeostasis, extracellular matrix accumulation and inflammation mechanism.