Manfredi founded the Accademia degli Inquieti (Academy of Unquiet) in Bologna around 1690 as a place where scientific topics could be discussed.

In 1704 he was named "Superintendent of the waters of Bologna", and was also made head of the college of Montalto, which educated young men destined for a clerical career.

[3] As a result of this discovery, the Church admitted the scientific nature of Galilean system and removed from the index many works of Galileo Galilei.

His poetic vein shows itself in a group of poems called "for a nun," inspired by the closure of the convent of Giulia Caterina Vandi, a girl of Bologna with whom Manfredi had fallen in love.

This group includes the song "Woman, they are your eyes", considered his masterpiece, and numerous sonnets in the style of Petrarch.