'diastereomer' originates from Greek elements, specifically 'dia-' + 'stereos' and 'isomeros', where 'dia-' meant 'apart', 'stereos' meant 'solid' or 'three-dimensional', and 'isomeros' (from 'isos' + 'meros') meant 'equal part'.

'diastereomer' changed from the related coinage 'diastereoisomer' and similar formations (e.g., German 'Diastereomer') used in 19th–20th century chemical literature and eventually became the modern English word 'diastereomer'.

Initially, it referred to an isomer differing in spatial arrangement that is not a mirror image; over time that specific technical meaning has largely remained the same in modern usage.