Background: Over the years, the governments conducted multiple interventions to address female genital mutilation. However, this inhumane practice continues because of several cultural and educational factors. Therefore, this study aimed to develop and validate school-based health education program for female students to raise their knowledge and change their attitude towards female genital mutilation. Methods: Quasi-experimental study was conducted to validate health education program by using a stepwise approach as the following: the content validity was assessed by academic experts (n = 15) using the suitability assessment of materials (SAM) tool; face validity was assessed by adolescent students (n=40) using a self-administered three-point Likert scale; and a pre-and post-intervention assessment of knowledge and attitude among adolescent students (n = 200) was done to evaluate the construct validity. Results: The content validity ratios were ranked above 60% by the experts. The face validity results also revealed excellent validity indices varying from 75 to 100 %. Additionally, there were statistically significant improvements in the mean knowledge and attitude scores (P< 0.001) post-intervention with huge effect sizes (d =6.38, and d =3.54 respectively). Conclusion: the validation process helps in assessing the relevance of health education program for greater acceptance and responsiveness by adolescent students and for ensuring more program implementation fidelity.