Reigning grand dukes are/were typically Royal Highnesses. The later grand dukes of Tuscany were also imperial princes of Austria and therefore were Imperial and Royal Highnesses.
The only other grand dukes of any appreciable quantity who were not sovereigns or the heads of grand ducal houses were the Russian grand dukes (the sons and male-line grandsons of the Russian emperors). They were Imperial Highesses as senior members of an imperial house.
The Russian grand ducal title is actually more properly translated as ‘grand prince’; this distinction is maintained in German where their title is Großfürst rather than Großherzog.