Background: Parents of children with Autism Spectrum Disorder (ASD) are an integral component of the healthcare system as they have a substantial role in providing care and support for their children. Therefore, implementing effective parent training programs is of paramount importance. Hence, parents feel self-assured in their capacity to navigate challenges that come with caring for their children with ASD. Purpose: This study aimed to determine the effect of health education program using an illustrated booklet on knowledge and practice of parents who have children with ASD. Design: a quasi-experimental pretest-posttest study design was used. Settings: This study was conducted at the Psychiatric and Neurological Outpatient Clinics of both Smouha Specialized University Hospital for Children as well as the Main University Hospital in Alexandria. Sampling: A convenient sample of 60 parents who were attending with their children having ASD in the previously mentioned settings. Instruments: Two instruments were used for data collection; Instrument one: Knowledge of parents having children with ASD interview scheduled sheet, and Instrument two: Parents' caregiving practices for their children with ASD. Results: revealed that 83.3% of parents of the study group exhibited good level of knowledge following the health education sessions with total mean score (5.27±0.91) compared to none of the control group (1.47±1.07) and the difference was statistically significant (p< 0.001*). Regarding caregiving practices, 76.7% of parents in the study group displayed a satisfactory level after the health education sessions with total mean score (25.11±8.20) compared to only 3.3% of the control group (11.40±1.54) with statistically significant difference (p <0.001). Conclusion: this study demonstrated the substantial positive impact of the well-designed comprehensive health education program on parents' knowledge, and subsequently their caregiving practices. Recommendations: Continuous health education and counseling programs should be launched for parents about the care of their children with ASD.