Manuela Santiago Collazo (born c. 1938) is a Puerto Rican politician who was the mayor of the city of Vieques.

Santiago Collazo became Vieques' first female mayor during the 1984 general elections. She had remained in that position until 2001.

A popular politician among Vieques residents and among many mainland Puerto Rico residents as well, Santiago Collazo has been met with various difficult moments during her tenure as mayor: In 1989, Vieques was one of the most severely affected Puerto Rican cities after the passing of hurricane Hugo. Large amounts of money were required to return the town to normality, as the island-city's boat service to Fajardo had to be temporarily stopped, the local airline, Vieques Air Link, suffered temporary loss of some of their aircraft, and the city lost electricity and water services. The city was later also affected by other hurricanes and storms.

In 1995, many important political figures wrote a letter to United States president Bill Clinton, asking to investigate an incident where an atomic bomb supposedly hit Vieques by accident in 1966. Santiago Collazo signed the letter and sent it to the president. It could be said that this was a small beginning to what would later become mass protests by Vieques citizens against the presence of the military there. After David Sanes' death by a military bomb in 1999, the protests intensified, and, by 2003, the military left the island of Vieques.

Santiago Collazo led a campaign to attract more airlines to Vieques' small airport facility; she has succeeded in part: whereas during the early 1980s only Vieques Air Link and Prinair provided service to the airport, now the airport is served by Vieques Air Link, Air Culebra and a number of other small carriers from around the rest of the Caribbean.

Manuela Santiago Collazo lost her bid for reelection to Damaso Serrano in 2001.