The house is estimated to be worth $19 million.
The protesters out up a banner on the roof of the mansion that called for Gaddafi to get "Out of Libya" and "Out of London".
Saif al-Islam is reported to have bought the home in the Hampstead Garden Suburb area of north London in 2009. The mansion, a four-storey house is up for sale on a local real estate website and has nine bedrooms, five reception halls, a jacuzzi, cinema and a swimming pool.
Police have made no arrests and have been reported as treating the occupation as a civil matter.
UK has already frozen assets of Gaddafi and his children and is mulling to support a no-fly zone over Libya planned by the US and other western countries to resist Gaddafi's use of military in crushing rebels.