'antisyphilitic' originates from the Greek prefix 'anti-' meaning 'against' combined with Neo-Latin 'syphiliticus' (from 'syphilis'), where 'syphilis' was the name given in Latin (from the 1530 poem by Girolamo Fracastoro) to the disease now called syphilis.

'antisyphilitic' developed by combining 'anti-' + Neo-Latin 'syphiliticus' (or 'antisyphiliticus') in medical Latin and entered English usage in contexts of 18th–19th century medical literature, eventually becoming the English adjective and occasional noun 'antisyphilitic'.

Initially it meant simply 'opposed to syphilis' (i.e., acting against the disease); over time it has been used more specifically to mean 'preventing or treating syphilis' when referring to drugs, treatments, or measures.