Their lives were saved by the "quick thinking" of paramedics on Monday, police said.
The deaths in Barnsley on Good Friday are not believed to be linked to two other drug-related deaths in West Yorkshire.
Toxicology reports are expected in the next few days.
Ch Supt Rob Odell, of South Yorkshire Police, said: "In addition to the deaths reported to police, on Monday we received two separate reports of individuals becoming gravely ill after taking suspected illegal substances.
"Thanks to the quick actions of paramedics, those individuals survived."
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He said one of the four South Yorkshire deaths was "potentially linked to a pre-existing medical condition".
However, detectives are keeping an "open mind" and the other deaths could be due to an "unusually strong supply, or something added to the drugs", Mr Odell said.
"We understand there have been further deaths in the West Yorkshire region that may also be connected to drugs use," Mr Odell said.
"We are in contact with West Yorkshire Police officers but at this stage, we do not believe the deaths are linked. We will keep an open mind as our investigations continue."
Police have appealed for anyone with concern or information to contact them, and to seek medical help if they have taken a substance and feel unwell.
Detectives investigating four drugs-related deaths in South Yorkshire have said two other people were taken "gravely ill".