Mr Sisi has faced heavy criticism over his executive decision to give away the Red Sea islands, during a visit by Saudi Arabia`s King Salman.
The uninhabited islands have been under Egyptian control since 1950.
The protesters in Cairo chanted "Sisi out" and "We own the land".
Mohamed Hussein, an engineer, told Reuters: "I`m protesting because of the overall situation in the country, not just the islands."
Some also chanted "The people want the downfall of the regime!" - a slogan from the 2011 Arab Spring uprising that toppled former leader Hosni Mubarak - as well as "Sisi - Mubarak".
At least 80 people were arrested in Cairo and Alexandria, officials said.