Background Flipped learning excessively boosts the conceptual understanding of students through the reversed arrangement of pre-learning and in classroom learning events and challenges students to independently achieve learning objectives. Using a gamification method in flipped classrooms can help students stay motivated and achieve their goals.  Methods This study adopted a randomized controlled study design with a pre-test and post-test and involved 128 nursing students at Mansoura University. This study randomly divided the students into the study and control groups. Data were collected at three time points using six tools. In the intervention group, Moodle was gamified for 6 weeks.  Results A significant difference in the students’ self-confidence (p = 0.021), skills knowledge (p < 0.001), intensity of preparation (p < 0.001), and motivation (p < 0.001) was observed between the two groups; however, no difference in the students’ skills performance (p = 0.163) was observed between the two groups after using gamified flipped classrooms. Conclusions Compared with the traditional flipped classrooms, gamified flipped classrooms improved nursing students’ motivation, intensity of preparation, skills knowledge, and self-confidence during laboratory clinical practice. Thus, gamification is a learning approach that can be implemented in conjunction with the flipped classroom model to motivate students to participate in the learning process. Trial registration. Prospectively registered with ClinicalTrials.gov on 26/04/2021; registration number NCT04859192.