The Legally Blonde actress was slammed by PETA after she was seen walking in Venice, California last week with a bag that was apparently made out of python skin, WENN reports.
"No matter how much Reese paid for that bag, the animals paid a much higher price," a spokesperson for PETA said.
The rep continued: "We can't imagine that she'd wish to contribute to this hidden suffering, especially for something as frivolous as a fashion accessory that can be replicated with no bloodshed.
"These days, it's easy to have a look that kills without killing, with fake snake, mock croc, python pleather, and other designer items that pay tribute to the beauty of these animals without massacring them," the spokesperson concluded.
Witherspoon recently joked that she would "make out" with Jennifer Aniston, praising the star's beauty and "complete lovability".
In September, the actress was taken to hospital after being hit by a car while jogging.
Witherspoon has since insisted that she will not press charges for the incident.