The primary use of papaya leaf in herbal medicine today is as a vermifuge, that is, to remove intestinal worms. Papaya leaf has less of the protein-dissolving papain than the fruit, so it is less likely to "dissolve" the worms, but it contains tannins that the fruit does not. These tannins protect the intestine from reinfection by "tanning" proteins in the lining of the intestinal wall so that worms cannot attach themselves.

Physicians of nineteenth century America used papaya leaf to treat "fermentative indigestion," a condition of bloating, nausea, and flatulence frequently following excessive consumption of fermented foods.