Treatments for the primary, secondary, and latent stages of syphilis are special preparations of penicillin, an antibiotic, called benzathine penicillin. This medication is injected into the muscle in a single dose in earlier stages of syphilis, and in several weekly doses in the late latent stage. Other combinations of penicillin preparations generally don't contain enough penicillin to be effective. For those who are allergic to penicillin, other types of antibiotics may be prescribed, but data to support the use of alternatives to penicillin is limited.

Neurosyphilis and ocular syphilis are treated with another type of penicillin preparation, called aqueous crystalline penicillin, which is administered intravenously or by infusion for 10 to 14 days. This treatment will prevent the disease from progressing, but it may not repair damage already done.

The treatment for tertiary syphilis depends on the organ systems affected.

In order to prevent the spread of syphilis, patients receiving syphilis treatment should abstain from sex until all syphilis-related sores are completely healed. They should also notify their sex partners so that their partners can also be tested and receive treatment if necessary.