Kate and Gerry McCann said they are “horrified” to learn that Sir Clement Freud, who befriended the pair following Madeleine's disappearance in 2007, is an alleged child sexual abuser.
The former Liberal MP and broadcaster, who died in 2009, has been accused of abusing a girl over several years who he brought up as a daughter.
He has also been accused of abusing another girl as a child and raping her when she was 18 years old.
Freud, who was 83 in 2007, had a villa in Praia da Luz, Portugal, which is the resort where the three-year-old went missing.
He became friends with the McCanns in the weeks following their daughter's disappearance, inviting them to his house on two occasions.
Detectives from Operation Grange, the Metropolitan Police investigation into the child's disappearance have been alerted to the fact that Freud had a villa nearby.
A source close to the McCanns told MailOnline: "It certainly raises a lot of questions. They will be appalled to hear the details."
Freud's widow, Jill Freud, 89, said she was “deeply saddened and profoundly sorry for what has happened to these women”.
Sylvia Woosley, who first met Freud when she was 10 and later went to live with him when her mother’s marriage broke down, claims in an ITV Exposure documentary that he molested her over several years.
A second woman, who wants to remain anonymous, alleged that the Liberal politician also abused her as a child and raped her when she was 18.
In the programme, due to be broadcast on Wednesday, Woosley, now in her late 70s, said: “I just want to clear things up before I die...I want to die clean.
“Having been so hard on myself, trying to destroy myself so many times, you can’t bury the truth forever, it needs to be heard.
“I don’t want to take this to my tomb. I would like to just return to the child I was before I was molested physically, before I was introduced to that side of life too early.”
She told the programme she first met Freud, known as Clay, when he was aged 24 and worked at the Martinez hotel in Cannes in the late 1940s. She was 10 and her family was living in the south of France.
Woosley claims that he kissed her on the mouth during a bus trip. She said: “I was disgusted and helpless. I just didn’t react in any way because I couldn’t. I didn’t know what to do.”
From the age of 14, when she lived with Freud and his wife in London for five years, she claims that he frequently molested her, even “playfully” touching her breast in front of his wife, although she believes Freud's wife had no knowledge of the abuse.
Later, aged in her early 40s, Woosley said she confronted Freud at the House of Commons and asked why he had abused her. She says he replied: “Because I loved you. You were a very sensual little girl.”
The second woman said that she first met Freud in 1971 at her family home as a “lonely, neglected and socially isolated” 11-year-old.
Then a celebrity, he would call her on the phone and tell her she was special and intelligent, and was treated as a surrogate father figure by her parents, she said.
Two years later, after he was elected as an MP, he would take her on trips to Parliament and his home, and would kiss her on the mouth and hug her.
She said: “I felt sick but grateful at the same time. Frightened and unable to move or react in any way.”
When she was 14, she claims Freud asked her and another friend of the same age: “Would you like to get naked and have some fun?”
Four years later, in June 1978, when she was 18, the woman alleges that he came over to her parents’ flat and “brutally and perfunctorily” raped her.
She told the broadcaster: “I live in constant terror that I’ll be found out, exposed. I’ve already suffered across nearly 40 years. It’s not simply to be labelled as depression or mental illness, this is disempowerment, self-destructiveness and grief. This is what real suffering looks like.”
Writer, broadcaster and politician Freud, who died at his desk aged 84 in 2009, first became a household name in the 1960s and 70s in Minced Morsels dog food adverts.
A celebrated food, sport and comment print journalist, he also enjoyed a long career as a television and radio personality, regularly contributing to Radio 4’s Just A Minute for 30 years and featuring on shows including Have I Got News For You.
ITV said two of Freud’s children had viewed the documentary before broadcast on their mother’s behalf.
Mrs Freud said: “This is a very sad day for me. I was married to Clement for 58 years and loved him dearly. I am shocked, deeply saddened and profoundly sorry for what has happened to these women. I sincerely hope they will now have some peace.”
A spokesperson for the Liberal Democrats said: “These allegations are horrific. We are desperately sorry to learn that lives have been ruined by a man whose public face was so greatly at odds to his true character. It has clearly taken a lot of courage for these women to speak out, after a lifetime of having to hide it.
“This is the latest in a terrifying line of cases where high profile figures have systematically used their status, celebrity and power, to abuse and to rape.
“Clement Freud was a senior figure in the Liberals, our party’s predecessor, and we are deeply shocked and horrified by this news. Our party was never aware of what happened, and our hearts go out to the women who were affected.”