There is growing concern about the health effects of school classroom environments, where children spend long periods of time. However, little is known about the impact of multiple design features on children. This study used a virtual reality experimental approach to investigate the effects of classroom design characteristics on children's physiological and psychological outcomes. Ninety-six school-aged children (aged 10–14 years) experienced classroom environments using virtual reality technology and the restorative effects of seven design characteristics in different combinations were tested. The children's stress, attention, mood, and restoration were measured using physiological indicators and questionnaires during and after the experience. The results showed that six design characteristics had a significant effect on children: indoor plants, window views, seating arrangements, window areas, wall decorations, and wall and furniture colors. The effects and strengths of the different design characteristics varied. However, spatial density did not appear to have any effect. The results also revealed significant differences in cognitive and emotional perceptions according to gender and age. The need for future longitudinal experiments with long-term, real-life scenarios is discussed. The research findings can inform evidence-based design, guidelines, and standards for healthy school environments.