'non-peptide' originates from Latin, specifically the word 'nōn' meaning 'not', combined with the modern English chemical term 'peptide', which ultimately derives from German 'Peptid' and Greek 'peptós'/'pēpsis' meaning 'digested'/'digestion'.

'Peptid' entered English as 'peptide' in the late 19th century; the privative prefix 'non-' was later added to form the modern English term 'non-peptide' to categorize compounds outside the peptide class.

Initially, it meant 'not a peptide' in chemical classification, and this sense has remained stable, expanding in use to describe non-peptide drugs and ligands.