In the post-pandemic era, our health is facing unprecedented challenges, and people are more willing to obtain health-related information or interact with each other than ever before. In this context, people’s interest in mindfulness information is also growing. However, not enough attention has been paid to the relationship between mindfulness information design and information interaction. The purpose of this study is to assess the impact of information design based on the gain and loss framework on people’s willingness to interact with mindfulness information, and to identify the framework for achieving better results. Through two experimental studies, we find that information design based on the framework of gains and losses can produce different effects. Specifically, the findings of the first experiment (N = 282) shows the individuals are more willing to interact mindfulness information when they are exposed to gain-framed information rather than loss-framed. In the second experiment (N = 308), we find that loss framing, compared with gain framing, led to greater health risk perception, which in turn make participants more likely to interact with mindfulness information with others. Additionally, our results show that the lay theories of health plays a moderating role in the direct effect of information framework on willingness to interact with mindfulness information in social media. When individuals hold incremental lay theories, they are more willing to interact with mindfulness information under the gain-framed information condition compared with the loss-framed information condition. However, when individuals are in entity condition, there is no significant difference in the willingness to interact with mindfulness information between the gain-framed and loss-framed information. Our studies of integrating information framework into designing mindfulness information suggest a promising strategy of health information interaction in social media.