The 35-year-old hooker is the Springboks most capped player and guided his team to victory over England in Paris in 2007 to become world champions.
But, after an illustrious playing career and two seasons with Saracens, Smit has decided to hang up his boots and return to his native South Africa where he will assume a CEO role with The Sharks in Durban.
“It’s quite emotional to consider that something that has been at the very centre of my life for so long is suddenly about to end,” he said.
“A match between Saracens and the South African Barbarians is a fitting conclusion to my career.”
Flanker Andy Saull and full-back Joe Maddock will also make their final appearances in Saracens colours, while England international Mouritz Botha is set to start at No6.
The visitors, coached by Nick Mallett, include former Saracens forward Donald Barrell and England 7s international Matthew Turner in their squad.
Rugby returns to the City on Thursday 16 May when Saracens host the South African Barbarians at the Honourable Artillery Company on City Road. Tickets are available at www.saracens.com