The purpose of this study was to evaluate the effect of different metacognitive interventions on knowledge and regulation of cognition, as well as academic performance (i.e., exam and final grades) in three sections of an undergraduate human anatomy and physiology course. All targeted classes were randomly assigned to one of three groups (reflection practice, passive acquisition of knowledge, and collaborative learning), and the interventions were implemented after exam 1. A pre- and posttest survey was administered during the semester (during week 2 and after exam 2), and exam and final course grades were collected at the end of the semester. The final sample included 129 students. A significant interaction of group and time was observed for knowledge of cognition: it increased in the reflection practice group, did not change in the collaborative learning group, and it decreased in the passive acquisition of knowledge. The interventions did not produce any significant interactions or main effects on regulation of cognition, exam scores, or final grades. Along with more research on metacognition in physiology education contexts, it is recommended to further examine the ways in which such data can be collected, as self-report measures only tell part of the story.