With the development of autonomous technology, the research into multimodal human-machine interaction (HMI) for autonomous vehicles (AVs) has attracted extensive attention, especially in automotive wellness. To support the design of HMIs for automotive wellness in AVs, this paper proposes a multimodal design framework. First, three elements of the framework were envisioned based on the typical composition of an interactive system. Second, a five-step process for utilizing the proposed framework was suggested. Third, the framework was applied in a design education course for exemplification. Finally, the AttrakDiff questionnaire was used to evaluate these interactive prototypes with 20 participants who had an affinity for HMI design. The questionnaire responses showed that the overall impression was positive and this framework can help design students to effectively identify research gaps and expand design concepts in a systematic way. The proposed framework offers a design approach for the development of multimodal HMIs for autonomous wellness in AVs.