Izzie (voiced by Lara Jill Miller) is an average young girl with a constantly expanding assortment of interests. She also acts as the webmaster for the SciGirls website, which hosts a database of science videos following real-life SciGirls. This resource often comes in handy, because whenever Izzie encounters a tricky situation and she is able to zap herself into her computer and follow along with the girls' investigations. Afterward, she is easily able to design a solution to her own dilemma.
Jake (voiced by Greg Cipes) has known Izzie since they were in preschool and has remained her closest friend. He usually meets up with Izzie at school, online, or around the town. More often than not, Jake finds himself drawn into Izzie's scientific situations.