Anatomy and physiology courses are foundational in nursing education but are often perceived as challenging due to heavy content load. Innovative teaching methods, including social media platforms like Instagram Reels, may enhance student engagement and learning. In this quasi-experimental pre-post-test design with a control group, we examined the effectiveness of Instagram Reels in teaching human muscle anatomy to first-semester nursing students. Participants were divided into an experimental group (n = 83) that created and reviewed Instagram Reels on muscle anatomy and a control group (n = 53) that received a didactic lecture. Knowledge acquisition was assessed using faculty-developed multiple-choice tests administered before and after the intervention. Satisfaction, motivation, and perceptions were measured using validated questionnaires. Of the 83 students in the experimental group, 53 completed both a pre-test and post-test, while all 53 students in the control group did so. The experimental group showed a statistically significant increase in knowledge scores from pre-test (M = 55.19 ± 18.11) to post-test (M = 65.47 ± 20.03), t(52) = -3.007, p = 0.004. The control group showed no statistically significant change. The experimental group reported higher satisfaction levels (M = 7.72 ± 1.72) compared to the control group (M = 6.62 ± 2.00), t(134) = 3.411, p = 0.001. High learning motivation and positive perceptions of Instagram Reels were also reported. Male students in the experimental group reported higher satisfaction than female students, X[superscript 2](1, N = 83) = 8.64, p = 0.003. Integrating Instagram Reels into anatomy education significantly enhances nursing students' knowledge acquisition and satisfaction levels. Social media platforms with expert supervision can serve as effective educational tools to engage students and improve learning outcomes. Further research should explore gender differences in satisfaction with social media-based learning interventions.