Gissendaner was scheduled to die at 7 p.m. Tuesday, but her lawyers filed appeals to state and federal courts in her final hours to try to spare her life.
Her children had to make a heart-wrenching choice Tuesday: go see their mother one last time, or make a final appeal in front of the Georgia Board of Pardons and Paroles.
"We chose to try and save her life, and they still denied us," daughter Kayla Gissendaner said outside the state's execution facility in Jackson.
Even a recent letter on behalf of the Pope wasn't enough to sway the parole board.
So Gissendaner's legal team filed three appeals to the U.S. Supreme Court -- all of which were denied.
When Gissendaner finally walked to the execution chamber after midnight, she saw the witnesses through a window and began sobbing, witness Jeff Hullinger of WXIA-TV said.
She then made a final statement "apologizing to an amazing man that lost his life because of her," Hullinger said.
Gissendaner was convicted of murder for persuading her lover to kill her husband
in 1997. She became Georgia's first female prisoner to be executed in 70 years.
As Gissendaner was being executed, the Gwinnett Daily Post
reported, she sang "Amazing Grace."
Pope Francis weighed in
While waiting for an answer from the board, a representative for Pope Francis sent a letter saying that the Pope wanted the board to spare Gissendaner's life.
"While not wishing to minimize the gravity of the crime for which Ms. Gissendaner has been convicted, and while sympathizing with the victims, I nonetheless implore you, in consideration of the reasons that have been presented to your Board, to commute the sentence to one that would better express both justice and mercy," the letter read.
It wasn't clear whether the board saw the Vatican representative's letter. A spokesman for the board declined to comment, saying what happens inside the hearings is private.
This isn't the only U.S. case to draw the attention of Francis, who called for an end to the death penalty when he spoke to Congress last week.
His representative has also sent a letter to Oklahoma's governor, asking her to commute the death sentence for Richard Glossip
, who's scheduled to be executed there Wednesday.
The death row cases of Gissendaner and Glossip have something in common: Neither of the convicted murderers actually killed the victim.
In Glossip's case, the man who bludgeoned the victim to death testified that Glossip had hired him for the murder. That killer is serving a life sentence.
Douglas Gissendaner's family: He's the victim
The family of Gissendaner's slain husband, Douglas, said they had faith in the legal system.
"Kelly planned and executed Doug's murder. She targeted him and his death was intentional. Kelly chose to have her day in court and after hearing the facts of this case, a jury of her peers sentenced her to death," the statement read in part.
"As the murderer, she's been given more rights and opportunity over the last 18 years than she ever afforded to Doug, who, again, is the victim here," it said. "She had no mercy, gave him no rights, no choices, nor the opportunity to live his life. His life was not hers to take."
Inmate's children asked for mercy
But Kelly and Doug Gissendaner's children pleaded with authorities to show mercy.
"My dad would not want my mom to be executed, even knowing her role in his murder," Kayla Gissendaner said in an earlier statement. "He would not want us to endure another devastating loss."
The daughter has said her mother changed over the past 18 years.
"I had to face what my mom had done and find a way to forgive her," she said. "In the process, I saw that my mom had struggled through the years to come to grips with what she had done and face her own horror about her actions."
More than 90,000 people signed a petition
urging Gov. Nathan Deal to halt the execution, claiming the mother of three has turned her life around and calling her a "powerful voice for good."
"While incarcerated, she has been a pastoral presence to many, teaching, preaching and living a life of purpose," the petition states. "Kelly is a living testament to the possibility of change and the power of hope. She is an extraordinary example of the rehabilitation that the corrections system aims to produce."
Her lawyers have argued that Gissendaner's sentence was "disproportionate" compared to that of her co-defendant.
Gissendaner arranged to have her husband killed by Greg Owen, who stabbed Doug Gissendaner in the neck and back. Owen testified against Kelly Gissendaner as part of a plea bargain that got him a life sentence instead of death.
Execution postponed twice
Only 15 female inmates have been put to death in the United States since 1976, according to the Death Penalty Information Center
. The last woman executed in Georgia died in the electric chair in 1945.
Officials had previously set a date for Gissendaner's execution, but called it off in February due to inclement weather.
The constitutionality of lethal injection drugs has made headlines in recent years and European manufacturers -- such as Denmark-based Lundbeck, which manufactures pentobarbital -- banned U.S. prisons from using their drugs in executions in 2013. That meant 32 states had to find new drug protocols.
Last year, Oklahoma issued a moratorium
on executions after murderer and rapist Clayton Lockett convulsed, writhed and lay alive on a gurney for 43 minutes before dying. It was the state's first time using a new three-drug cocktail for an execution.
Message for her children: 'I love you'
Marcus Easley, a retired Chattanooga, Tennessee, police officer who was a friend and supporter of Kelly Gissendaner, told CNN affiliate WSB he met with her on Tuesday.
Gissendaner's children, he said, were not able to visit her in prison because they were making a case for her life.
"They gave the children the choice between coming and seeing their mother one last time, or going before the parole board and fighting for her," he said.
Easley said he met Gissendaner years ago while bringing students to her prison for prevention programs. "We just became very close and very good friends, and I support her, totally," he said.
Easley said he asked Gissendaner whether she had a message for her children.
"I love you, I love you, I love you. I am so proud of you," she said, according to Easley. Those were the last words he heard her say before he left.