The recent expulsion of four girls and suspension of three others was the second scandal to hit the Leadership Academy for Girls, which opened in 2007 to groom bright children from deprived backgrounds for a brilliant career. A dorm matron is currently on trial accused of abuse and sexual assault.
"I have made several mistakes and one of them was being overprotective of the girls, which has led to an impression that the school is isolating them from society," Winfrey was quoted as saying in the Weekend Argus.
She said she had also underestimated the extent of homesickness among girls at the boarding school.
Last month, four students were expelled and three others suspended. South African media at the time said they were accused of trying to force students into relationships and to engage in sexual contact.
Winfrey herself hasn't given details of the misconduct. But she said in the newspaper interview that it was "insulting" that the family of one of the expelled girls had complained to the press even though she had been warned before about her behavior.
"Those girls in their own testimony during the (disciplinary) hearing said they knew they were breaking the rules and that they deliberately broke the rules," the talk show queen was quoted as saying.
The institution just outside Johannesburg opened with a blaze of publicity in January 2007 with about 150 girls in 7th and 8th grades. The Academy is expected to grow by one grade each year until it reaches full capacity in 2011, with approximately 450 girls in grades 7 through 12.
Winfrey poured $40 million into the 28-building campus, which is spread across 22 lush acres. It has computer and science labs, a library, theater and wellness center, all protected by strict privacy. Each girl lives in a two-bedroom suite — a far cry from their humble surroundings at home.
It's the fulfillment of a promise Winfrey made to former South African President Nelson Mandela and aims to give poor girls a quality education and prepare them for leadership positions in a country where state schools are struggling to overcome the legacy of white-minority rule.
"The majority of girls are thriving, really fulfilling the dream and vision I had," Winfrey told the newspaper. "They really have exceeded any expectations I had for them."
"In spite of everything that's happened, what keeps me inspired and hopeful is the heart of every girl, because they are wonderful, they are magnificent."