A Soyuz capsule carrying Peake, 44, and two other crew members will land in Kazakhstan on Saturday.
During his stay, he made the first spacewalk by a British astronaut and remotely steered a robot on Earth.
He is the first person to visit space under the British banner since Helen Sharman in 1991.
Peake, Russian cosmonaut Yuri Malenchenko and US astronaut Timothy Kopra made their farewells and entered the Soyuz TMA-19M – the Russian space capsule that will carry them home from the ISS at about 3.35 a.m. on Saturday.
Speaking in his last live link-up from space, Peake said: “It’s been a fantastic six months up here – (a) really remarkable, incredible experience.
“I’m looking forward to coming home, looking forward to seeing my friends and my family, but I am going to miss this place (the ISS).”
While in the ISS, he ran the London Marathon strapped to a treadmill, held a science lesson for 300,000 schoolkids and ventured out of the space station on his first spacewalk.
“The first time I saw the Earth was just a few moments after insertion into orbit,” he told CNN last month in an interview from the ISS.
“It was just the most incredible feeling to be in orbit and see the planet for the first time. It was spectacular.”
While aboard the space station, the three conducted scientific research in biology, biotechnology and science.