<p>Histology education faces significant challenges due to its abstract content and compressed curricula, with limited comparative evidence on integrated active learning strategies across diverse student groups.</p><p>A quasi-experimental study at Babol University of Medical Sciences involved students from eight disciplines. Satisfaction was assessed via a 5-point Likert scale from 314 out of 373 active learning students (Flipped Classroom/FC, Small Group Learning/SGL, Teacher Role-Playing/TRP) and 213 out of 365 traditional teaching students. Academic performance was compared using final exam scores from all active learning (<i>n</i> = 373) and traditional (<i>n</i> = 365) students over five semesters.</p><p>Satisfaction was significantly higher in all active learning groups compared to traditional teaching (3.468 ± 0.067; <i>p</i> &lt; 0.0001). Flipped Classroom achieved the highest satisfaction (3.974 ± 0.051), but didn’t show significantly difference with other active groups (Small Group Learning (3.920 ± 0.051, and Teacher Role-Playing (3.897 ± 0.056). Satisfaction correlated with improved motivation, retention, and comprehension. Male students reported higher satisfaction. Teacher Role-Playing satisfaction varied significantly by discipline (<i>p</i> = 0.026), being highest in Anatomical Sciences and lowest in Speech Therapy. Academic performance was superior across active learning groups, with the greatest gains among graduate students (<i>p</i> = 0.0285) and in medium/large classes (<i>p</i> &lt; 0.0001).</p><p>In conclusion, the integrated active learning strategies significantly enhance both student satisfaction and academic achievement in histology education. Effectiveness is moderated by gender, discipline, academic level, and class size, supporting the adoption of tailored, student-centered approaches to address engagement and curricular challenges in health sciences.</p>