Hedren was born on January 19, 1930, in New Ulm, Minnesota, to Bernard Carl and Dorothea Henrietta (nee Eckhardt) Hedren. For much of her career, Hedren's year of birth was reported as 1935. In 2004, however, she acknowledged that she was actually born in 1930 (which is consistent with the birth registration index at the Minnesota Historical Society). Her paternal grandparents were Swedish immigrants, while her maternal ancestry is German and Norwegian.

In 1952, Hedren met and married 18-year-old future advertising executive Peter Griffith. Their daughter, actress Melanie Griffith, was born on August 9, 1957. They were divorced in 1961. On September 22, 1964, Hedren married her then-agent Noel Marshall, who later produced three of her films; they divorced in 1982. In 1985, she married steel manufacturer Luis Barrenechea, but they divorced in 1995. Hedren was engaged to veterinarian Martin Dinnes from 2002 until their breakup in mid-2008. In September 2008, Hedren told The Sunday Times "I'm waiting for someone to sweep me off my feet."  Hedren played a role in the development of Vietnamese-American nail salons in the United States. In 1975, while an international relief coordinator with Food for the Hungry, she began visiting with refugees at Hope Village outside Sacramento, California. When she learned the women were interested in her manicured nails, she employed her manicurist to teach them the skills of the trade and worked with a local beauty school to help them find jobs. Hedren's work with the Vietnamese-Americans was the subject of Happy Hands, directed by Honey Lauren, which won Best Documentary Short at the Sonoma International Film Festival in 2014. CND and Beauty Changes Lives Foundation (BCL) have announced the BCL CND Tippi Hedren Nail Scholarship Fund to support professional nail education and will be administered starting January 1, 2014.  Hedren suffered from severe and persistent headaches for a long time and therefore was unable to accept several projects, including a television series produced by and starring Betty White. After she got a titanium plate put in her neck, she improved and then agreed, with the blessing of her doctor, to take the part of a dying woman in the soap opera Fashion House. While she was rehearsing a scene, a gallon of water fell from the ceiling onto her head. The headaches returned after the incident and persisted. Hedren filed a suit to receive recompense following her inability to work. Hedren's lawyer, Joseph Allen, made a mistake in his discussions with the defendants that allowed them to block him from filing suit. Hedren sued Allen for malpractice. In 2013, The Hollywood Reporter reported that Hedren had been awarded a $1.5 million settlement, including $213,400 for past lost earnings and $440,308 for future lost earnings, against her former lawyer. Hedren was hurt by the report since she had not collected the award. She gave an interview to explain that her former lawyer does not have the money to pay her, and discussed how the report put her in a difficult situation since her foundation was in dire need of funds. She explained that she has to raise $75,000 monthly just to keep it going. "Chances are I won't ever even see the money, and that what hurts so badly, that in all of this pain and suffering that publication ran with a swift and not researched story, which told people around the world who have been so gracious and thoughtful about sending donations, that I no longer needed them."

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