Oprah school employee accused of sexually abusing girl pupils
At least seven alleged victims have submitted statements about the 27-year-old woman, police said.
"Several charges including alleged assault, indecent assault and soliciting girls under age to perform indecent acts are being investigated against her," a spokesman said.
The woman is expected to appear before a magistrate on Monday.
Winfrey's 20 million leadership academy near Johannesburg has been dogged by controversy since opening in January, with a launch attended by Mariah Carey, Tina Turner, Sydney Poitier and Spike Lee.
The US talk-show host selected the first class of 152 poor, mostly black, pupils to attend the school that boasts state-of-the-art facilities including laboratories, a yoga studio and beauty salon. Tuition and board is free. The academy provides its 450 students with textbooks, uniforms and meals.
In March, some parents complained the school was too strict, with its limits on visits, phone calls and e-mail contact comparable to rules in prisons.
In May, others complained their children were not allowed junk food and, when they visited the school, they had to go through a security gate.
After the latest controversy, Winfrey was reported to have flown to meet parents and school officials.