It is the first time humans have been infected by the parasite in Australia.
It is believed the couple became ill after eating a fish they caught on a camping holiday.
Alfred hospital infectious disease physician Andrew Fuller said that when the couple ate the fish, believed to be a black bream, they also ingested the gnathostomiasis larvae.
"The worms are 1-3mm long and have got these sharp little teeth and they can go anywhere they like in the body," Dr Fuller said.
The worm works its way around the human body until it dies or is killed by the immune system.
"They move under the skin and cause itchy lumps that can make you feel sick - and it can be very hard to diagnose."
The infected couple suffered muscle pain, fevers, vomiting and their skin began to look like orange peel.
They were given antibiotics and have recovered.
The worms can stay in a human for 15 years, leaving people chronically ill.
They can make their way into the brain, other organs and the spinal cord.
"They eat your tissues," Dr Fuller said.
He had treated 28 people with the condition, who all contracted it overseas.
Neither of the latest patients had been overseas.
Dr Fuller sent samples of their blood to Bangkok.
The fish was caught in the Calder River, north of Derby, and the incident was reported in The Australian Medical Journal.