This article details a 'puzzling' teaching and learning method to engage undergraduate nursing (BSN) and exercise sciences (BSES) students in physiology or medicine Nobel Prize-winning discoveries, while reviewing course material through the "Puzzling Physiology and Nobel Laureates" (PPNL) game. The qualitative evaluations of 117 undergraduate BSN and BSES students revealed that 95% and 96%, respectively, agreed the game provided an opportunity to utilize critical thinking and problem-solving skillsets. Moreover, 96% of the 117 anonymous student respondents voted on increasing the number of PPNL game sessions per semester, and 94% agreeing the gamified learning strategy should be offered in subsequent classes as well. Interestingly, nearly 90% agreed that the learning experience was 'fun', and that it increased awareness of physiology and/or medicine discoveries. The style of the "Puzzling Physiology and Nobel Laureates" game lends to its reproducibility in a wide array of physiology courses for both majors and nonmajors.