Mthethwa issued a statement on Wednesday questioning the impact of frequent club sales on the development of the game of football and the welfare of players.
The changing of hands of PSL franchises has become a norm in South African football, with Tshakhuma Tsha Madzivhandila already sold a little over six months since replacing Bidvest Wits in the top-flight.
In a statement released by the Department of Sport, Mthethwa said the ongoing changes of ownership in the PSL is affecting the development of the game.
"While I fully appreciate the fact that new investors coming into sport club ownership is both a growing global phenomenon and indeed welcome, its impact on the welfare of the sport, its fans, players and supporting staff can be devastating if not properly managed and overseen," he said.
The statement added: 'There have been reports of players and staff often left in the dark when these transactions are completed and their employee rights violated.
'The Minister is aware of the media reports that Tshakhuma Tsha Madzivhandila (TTM) football club has been sold to new owners and while he has no interest in meddling in the private business transactions between buyers and sellers in a free market, he is worried about the plight of the players and staff.
'Minister Mthethwa has appealed to the South Africa Football Association (SAFA), the mother body and ultimate controlling entity and custodian of football, to ensure that the players and staff are treated in line with the laws that govern employer/employee relations in the country.
'The Minister will be monitoring the developing situation with keen interest.'