Children at the Malerato Centre for Hope in Mamelodi township outside Pretoria complained of stomach ache shortly after lunch on Thursday, according to police spokesman Tsekiso Mofokeng.
"Twenty kids were admitted," he said.
"A woman 35 years of age was arrested on suspicion of poisoning and charged with assault with the intent of causing grievous bodily harm," he told AFP.
Eight children were discharged later.
The centre houses 42 abandoned children as well as orphans whose parents died from AIDS, according to South Africa's Sunday Times.
"We were so worried. They were vomiting and crying. They had runny stomachs and were so sick," she said.