It's understood Portuguese officers will take the lead in the interviews, but British police will also be present.
Eleven people will be spoken to in total and it's hoped they could have information to help the case along.
Madeleine disappeared more than seven years ago whilst on holiday with her Catholic parents in the Algarve resort of Praia da Luz.
The toddler, then aged three, was taken from her hotel room on May 3 2007 as her parents dined at a nearby tapas restaurant with friends.
Portuguese police launched an investigation but ended it in 2008. The Metropolitan Police launched their own operation three years later.
Scotland Yard says it will not provide a "running commentary" on the inquiry but it's understood one of the people to be questioned will be Robert Murat.
He is not a suspect but was questioned at the time of Madeline's disappearance and has since been cleared of any wrongdoing.
Police are expected to question two other British people and seven Portuguese citizens.
According to reports police from the UK have supplied more than 250 questions for Portuguese police to ask the 11 witnesses.