Pienaar has won 57 caps for his country since making his debut in 2002, and represented them at the World Cup they hosted in 2010.
"After having given more than ten years’ service to the national team, I am now at a stage where physically I am struggling to balance the demands of playing in England with the number of games required by South Africa", he told the Everton website.
"I am proud to have represented and captained my country", he continued.
"There is a lot of very good young talent coming through and perhaps it is time for them to be given an opportunity. I wish the coaching staff and the players all the very best for the future."