The answer to this depends to some extent on who you see as a "major" historical figure and who is just a minor figure.
There are two people portrayed in the film who are clearly major historical figures, at least in the United States. These are the two presidents who are portrayed in the film. They are Martin Van Buren and John Quincy Adams.
Past that, it is less clear who is a major historical figure. Queen Isabella II of Spain is seen in the movie. So is the important abolitionist figure Lewis Tappan. Roger Sherman Baldwin was a governor and a US Senator. Cinque himself can be seen as a major historical figure because of his role in the Amistad incident.
You will need to decide for yourself which of these people are "major" figures in history.
The primary actor and major figure is John Quincy Adams, former President of the United States and the attorney who argued the case of the Amistad prisoners before the U.S. Supreme Court. The part is played by Anthony Hopkins. Nigel Hawthorne played Martin Van Buren, President of the United States. Arliss Howard played John C. Calhoun, who famously defended slavery. David Paymer played John C. Forsythe, Secretary of State under President Van Buren. Matthew McConaughey played Roger Sherman Baldwin, the trial lawyer who originally defended the Amistad prisoners. Having written all that, one would be well advised to take the Amidstad story line with a substantial grain of salt. Historians have noted a number of historical accuracies written in to make the story line entertaining.