Science, Technology, Engineering and Mathematics (STEM) education is increasingly important. Its importance can be separated into four dimensions. In design education, especially fashion design, STEM education is rare. In accordance with interest theory, this study examined the correlation between design self-efficacy, design interest, and learning effectiveness. An experiment was conducted in a department of fashion design at a technology college in Taiwan. Over four weeks, participants spent two hours weekly learning STEM topics related to fashion design and how to apply them in design practice. Data from questionnaire responses of 197 participants were used to test our research model. Results indicate that participants with higher design self-efficacy had stronger design interest (e.g., enjoyment and engagement). Moreover, better STEM learning was correlated with stronger design interest. In addition, design self-efficacy was positively correlated with STEM knowledge and it is mediated by design interests. Therefore, this study suggests that among students, learning STEM subjects increases design self-efficacy.