She said, "I may be in the USA but I have not forgotten my roots in Wales.
"My childhood in Wales was a very happy one. However, I know that not all children are so lucky and I therefore want to do all I can, especially as a parent myself, to help keep them free from harm."
Zeta-Jones has two children with husband Michael Douglas - Dylan, five, and Carys, two, and recently built a £2m second home in Swansea.
She said, "Wales is still my home and I am delighted to be part of the NSPCC's very important work across the country."
The Big Bike Ride aims to bring families together, regardless of age or fitness levels, to organise their own bike rides and raise money for charity.
Jo Carter, NSPCC Big Bike Ride co-ordinator, said, "It does not matter whether you plan to cycle the length of the country, or just enjoy an afternoon ride around the local park; it is the taking part that counts."
A whole host of celebrities will be joining the charity on the weekend from June 30 to July 2, including ex-Olympic cyclist Chris Boardman.