Prospero Colonna may refer to several members of the Colonna family:
- Prospero I Colonna (c. 1410–1463), Italian Roman Catholic cardinal
- Prospero II Colonna (1662–1743), Italian Roman Catholic cardinal
- Prospero Colonna (condottiero) (1452–1523)
- Prospero Colonna di Sciarra (1707–1765)
- Prospero Colonna di Paliano, mayor of Rome in 1899–1904
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