Police allege Jolly Shaju, 47, admitted poisoning her first husband, his parents, her current husband's ex-wife and two others between 2002 and 2014.
Her youngest alleged victim was just an infant when she died in 2014.
Mrs Shaju was remanded in custody until 16 October with two other suspects accused of being her accomplices.
One of them, Prajikumar, a goldsmith accused of supplying the cyanide, said he was innocent of all charges, according to the Press Trust of India (PTI). He said he had thought she was buying it to poison rats.
The case only came to light after Rojo Thomas - the brother of her first husband Roy Thomas, who died in 2011 - raised concerns with officials two months ago.
Mrs Shaju's first alleged victim was her mother-in-law, Annamma Thomas, who is said to have died after eating a meal prepared by her in 2002.
Six years later, Tom Thomas - Mrs Shaju's 66-year-old father-in-law - died under similar circumstances.
This was followed by the death of Roy in 2011. On this occasion, a post-mortem found traces of cyanide; however, it was not pursued.
In 2014, Annamma's brother Matthew insisted a second post-mortem be carried out on his nephew. He died the same year, PTI said.
The family became more worried in 2016, around the time of the death of their cousin Scaria Shaju's wife. Her young daughter, Alfine, had died two years earlier.
The suspect went on to marry Mr Shaju.
Police allege Mrs Shaju, who they say confessed to all six killings, was motivated by money. Her sister-in-law Renji said she had taken control of the family finances after her mother's death. Her father, she said, considered her the model daughter-in-law.
"I used to consider Jolly as my elder sister," Renji told PTI. "I used to like her. She used to behave in a friendly manner with everyone."
Police investigations are ongoing.