"I was an only child and it was lonely," the star said in an interview with InStyle magazine. "Some people love it and thrive on the independence, but I want my kids to have other kids around.
"Maybe two kids so they can run around life together like Rusty and Aubrey Griswold from (National Lampoon's) Vacation. So however that's going to come about, it's gonna happen."
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Despite her desire to expand her brood, Drew admitted that parenting is "a lot of pain and a lot of nervousness".
"I love the person who said, 'Parenting is like wearing your heart on the outside of your body'. It's the most beautiful, perfect analogy," she said.
"I have anxieties about how much I'd like to get it right, making sure I provide her with an environment that's safe, nurturing and loving. And silly and free, also consistent and grounding."
She added, "Then I just have the same typical fear every other parent has: Are they going to fall down?"
Drew, 38, started dating art consultant Will — the son of former Chanel CEO Arie Kopelman — in early 2011, and the couple announced their engagement in January 2012. They tied the knot in Montecito, Caliornia on 2 June, 2012.
Three months later, on 26 September 2012, Drew gave birth to their first child, Olive Barrymore Kopelman.
The Grey Gardens actress is currently filming her new movie, The Familymoon. Also featuring her 50 First Dates co-star Adam Sandler, the film tells the story of a man and women who are stuck at a South African resort for families after a bad blind date.