This study explored the self-regulation strategies and learning experiences of undergraduate science students completing Learner-Generated Digital Media (LGDM) assignments that had been implemented using a theory-driven, systematic approach. The rationale for using LGDM in science education is to facilitate student learning of complex scientific concepts through the multimodal representation of content using digital media. The study was conducted in seven science subjects from first to third year in Autumn 2017, using a sample of 348 undergraduate science students attending a university located in Sydney, Australia. All the participants were enrolled in subjects that required them to communicate complex scientific concepts using digital media. Training on LGDM was conducted online (n = 199) and in blended mode (n = 149). The study used a mixed-methods approach with a validated self-regulation questionnaire, LMS logs, assessment scores, group contribution data, open-ended questions, and interviews. Online students were more likely than blended students to report using self-regulation strategies for goal setting, time management, task strategies, and help-seeking. Data triangulation revealed that participation in LGDM assignments was perceived by students to contribute to their science content knowledge, provide them with digital media skills, and nurture their capacity for working in groups. The findings of this study have implications for how LGDM is deployed in science education.