Large groups in society, in particular people with low literacy, lack the necessary proactivity and problem-solving skills to be self-reliant. One omnipresent problem area where these skills are relevant regards filling in forms and questionnaires. These problems could be potentially alleviated by taking advantage of the possibilities of information and communication technology (ICT), for example by offering alternatives to text, interactive self-explaining scales and easily accessible background information on the questionnaires' rationale. The goal of this paper was to present explorative design guidelines for developing interactive questionnaires for low-literate persons. The guidelines have been derived during a user-centered design process of the Dutch Talking Touch Screen Questionnaire (DTTSQ), an interactive health assessment questionnaire used in physical therapy. The DTTSQ was developed to support patients with low health literacy, meaning they have problems with seeking, understanding and using health information. A decent number of guidelines have been derived and presented according to an existing, comprehensive model. Also, lessons learned were derived from including low-literate persons in the user-centered design process. The guidelines should be made available to ICT developers and, when applied properly, will contribute to the advancement of (health) literacy and empower citizens to fully participate in society.