'alpha-1-antitrypsin' originates from modern medical nomenclature, combining 'alpha-1' (referring to the protein's position in serum protein electrophoresis) and 'antitrypsin', which derives from the prefix 'anti-' meaning 'against' and 'trypsin' (the protease), where 'anti-' meant 'against' and 'trypsin' referred to the digestive enzyme 'trypsin'.

'antitrypsin' developed from earlier mid-20th-century terms such as 'alpha1-antiprotease' and references to 'alpha-1 globulin'; over time the term standardized to 'antitrypsin' and was combined with the electrophoretic designation 'alpha-1' to form 'alpha-1-antitrypsin'.

Initially it was named as an inhibitor 'against trypsin' in a general sense, but the meaning evolved to denote a specific serine protease inhibitor (now known as alpha-1-antitrypsin) produced by the liver that primarily protects lung tissue.