He was the son of Girolamo Colonna, a philologist and antique dealer who was also editor of the fragments of the Latin poet Ennius.

He suffered from epilepsy, which prevented him from practicing law, so he turned to studying the ancient authors of medicine, botany and natural history.

The publication of his first works on botany, such as De purpura made him a celebrity among naturalists and one of the first members of the Accademia dei Lincei in Naples, which had been founded by Federico Cesi in 1612.

Colonna became interested in the recently invented telescope and microscope, corresponding with Galileo Galilei and other Lincean academics on astronomy.

Colonna was a pupil of Ferrante Imperato and a friend of Giambattista della Porta and Bartolomeo Maranta.