Pennyroyal was commonly used as a cooking herb by the Greeks and Romans. The ancient Greeks often flavored their wine with pennyroyal. A large number of the recipes in the Roman cookbook of Apicius call for the use of pennyroyal, often along with such herbs as lovage, oregano and coriander. Although still commonly used for cooking in the Middle Ages, it gradually fell out of use as a culinary herb and is seldom used so today.

Even though pennyroyal oil is extremely poisonous, people have relied on the fresh and dried herb for centuries. Early settlers in colonial Virginia used dried pennyroyal to eradicate pests. Pennyroyal was such a popular herb that the Royal Society published an article on its use against rattlesnakes in the first volume of its Philosophical Transactions in 1665.

Pennyroyal tea is the use of an infusion made from the herb. The infusion is widely reputed as safe to ingest in restricted quantities. It has been traditionally employed and reportedly successful as an emmenagogue (menstrual flow stimulant) or as an abortifacient. Pennyroyal is also used to settle an upset stomach and to relieve flatulence. The fresh or dried leaves of pennyroyal have also been used when treating colds, influenza, abdominal cramps, and to induce sweating, as well as in the treatment of diseases such as smallpox and tuberculosis, and in promoting latent menstruation. Pennyroyal leaves, both fresh and dried, are especially noted for repelling insects. However, when treating infestations such as fleas, using the plant's essential oil should be avoided due to its toxicity to both humans and animals, even at extremely low levels.