Today, she's married, stepmum to her tattooed biker welder husband's three kids and back on screens in a romantic comedy.
It's quite a turnaround, especially for an actress who used to believe marriage was a 'death sentence'. So what changed?
"I had everything I wanted, not realising that maybe I was going after things that weren't filling me up in the way I wanted to be filled up," she says, candidly, when we meet in a London hotel to discuss her role as an unlikely bride in The Proposal.
"I never felt I was missing anything ever until one day I stopped long enough to smell the roses outside of this little treadmill I had gotten myself onto and I realised there were other things I liked, that I didn't know.
"I realised I didn't want certain things in my life that I got rid of and it opened the door to a plethora of other things that entered, but had I not stopped and done the work, I never would have appreciated or seen them."
In short, she fell in love with the right guy.
Sandra met Jesse, apparently a real-life descendent of the American outlaw, and former presenter of the Discovery Channel's Monster Garage, when she arranged for her godson to meet him for a Christmas present.
They started dating and three months in, she realised he was 'the one' - when he lay injured in a hospital bed after a racing accident.
"I always thought marriage meant that someone was going to ask you to stop being who you were and I met someone who not only wants me to be who I am, but likes it," says Sandra, beaming broadly.
"So my life changed in that my views towards marriage stopped being morbid. I found I was ready to be a good partner where I don't think I was a good partner to people before."
In a bizarre case of art imitating life, Sandra's character in The Proposal, Margaret, is a workaholic boss, who doesn't think she needs anything else in her life.
But when the threat of deportation back to her native Canada means losing her job as an editor in a publishing company, she turns to her personal assistant Andrew (Ryan Reynolds) and blackmails him into marrying her.
Andrew reluctantly agrees, on the condition that she flies with him to Alaska to meet his family and celebrate his Grandma Annie's (Betty White) 90th birthday.
In real life, of course, Sandra is nothing like the hard-nosed, Christian Louboutin-wearing New Yorker Margaret.
Although, she does look immaculate today, in a white and black one-sleeved top, with her long dark hair tucked behind one shoulder to reveal a diamond earring.
And she is the 'older woman'. While Ryan, married to Scarlet Johansson, is 32, Sandra will be 45 later this month - although she hardly looks a day over 29 - the age she was in her breakthrough role in 1994's Speed.
As she sucks on boiled sweets and lets out real belly laughs, it is clear she couldn't be an 'evil witch' if she tried.
Through roles in films like Miss Congeniality and Two Weeks Notice, Sandra - Sandy to her friends - became known as the comic actress who could play the girl-next-door, the tomboy and the sexy leading lady.
But the truth is she had some bad experiences of comedy and only agreed to do The Proposal if she could be executive producer.
"I was so reticent to ever do romantic comedy again, I just assumed it was always going to be bad and get screwed up," she explains.
"So as a protecting agent for myself, I said I would like to be an executive producer, just so I had the right to come in and meddle in case I didn't like what was going on, but I never had to do that, that's how much I enjoyed myself."
She's full of praise for The Proposal's zany female director Anne Fletcher and her co-star Ryan, who's been a friend for nine years.
You'd think it would have been awkward for the pair to film an hilarious full-frontal nude scene but Sandra laughs it off, claiming a scene where she had to rap and dance was "much harder" than being naked with Ryan.
She adds that she was content to take her clothes off for the comedic effect.
"I don't look at my body and go 'this is a machine, it's a beautiful specimen, I cannot show it in a funny light' - it's funny every day.
"I look at it every day and somewhere, there's something funny going on, so I saw that it could be used as a vessel in this film in a good way.
"I felt this was the time for me to do full nudity in a way I was comfortable with, in humour. I've done those scenes that are supposed to be sexy and they're just not."
However funny the scene, it's hard to ignore that Sandra - hidden by little more than a flannel - looks incredible in her birthday suit.
"I am always in various stages of shapes for work - if the woman needs to be more soft, I've gained weight and then I'll lose weight for another film where I wanted her wirey," she says.
"I enjoy using my body as something that helps me get into character. In this business, you get paid to work out and I can afford it, because I've had to hire somebody that will beat me to where I want to go."
As happy as she seems to chat about her body and aspects of her private life, Sandra's acutely aware that her marriage to Jesse has subjected him to the downside of fame.
They spend most of their time in Austin, Texas, where she also runs a restaurant, away from the prying eyes of Hollywood.
"Sadly, the nature of what I do brings notice to people who have no desire to be in that spotlight and it can destroy lives.
"I married an average Joe, who normally would be fixing your car and people would look down on what he did, but I know how extraordinary he is and I'm thankful that with all the attention, he's still OK being with me."
As for her acting future, Sandra implies that she might not stick at it for the long haul, unlike her 87-year-old Proposal co-star Betty White.
"I love to work, I'll always be working in some capacity, but it probably won't be in this business. Most of what I do in my life doesn't happen in front of the camera and I love it just as much."
Extra time - Sandra Bullock
Sandra was born in Virginia to a German, opera-singing mum and a voice-coach father. She spent much of her childhood flying between the States and Europe, where her mother was performing, and is fluent in German.
Her mother, Helga, died of cancer in 2000 at 63. She has said her mother's death inspired her to "accomplish things and savour the moment".
With her father and sister she runs her own production company, Fortis Films, which is producing her next film All About Steve, which stars Sandra and Bradley Cooper.
She is stepmother to her husband Jesse James's three children, Chandler, 15, Jesse Jr, 12, and daughter Sunny, 5.
Sandra has been nominated for two Golden Globe awards for her roles in rom-coms While You Were Sleeping and Miss Congeniality.