American girls Lindsay (Ashley C. Williams) and Jenny (Ashlynn Yennie) are traveling through Europe, and are enjoying their time spent clubbing and sightseeing. When their car breaks down during the road trip, they find themselves what appears to be an empty house to stay in for the night. When they wake the next morning, however, they discover that the house wasn't empty. Instead, the meet a Japanese man named Katsuro (Akihiro Kitamura), who, like the girls, has been captured inside of this house. The group meets Dr. Heiter (Dieter Laser), a retired surgeon. Dr. Heiter used to be well known for his ability to separate Siamese twins, but now he has an opposite, sinister plan - he wants to make what he refers to as a human centipede, meaning that he wants to connect people together. After stumbling upon something worse than any of them could ever imagine, can Lindsay, Jenny, and Katsuro find a way our of this nightmare?