Good oral hygiene is essential for schoolchildren's well-being. However, lack of knowledge, negative attitudes, and poor oral hygiene practices may predispose to oral-related diseases. This study aimed to examine the effectiveness of a nurse-led oral hygiene program on schoolchildren's knowledge, attitudes, and practices. A quasi-experimental design with pre-and-post-test was used. Using the convenience sampling technique, we recruited 400 schoolchildren, aged 11-12 and in grades 5-6, from two primary schools in Egypt. The study was conducted from September 2022 to May 2023. The Oral Hygiene Program served as the primary intervention. This program contains health education topics (e.g., the importance of oral hygiene, techniques for effective tooth brushing, and dietary choices that promote dental health). Three visits were conducted (Visit 1: introduction of the program purpose and objectives and pre-test scores collection, Visit 2: implementation of oral hygiene topics, and Visit 3: post-test scores collection). We used three self-report instruments (Oral Health Knowledge Questionnaire, Hiroshima University's Dental Behavioral Inventory, and Oral Health Practice Questionnaire) for pre- and post-test. Paired T test and Pearson correlation analysis were used for data analysis. After the intervention program, the oral hygiene program effectively enhanced schoolchildren's knowledge, attitudes, and practices. The post-intervention mean scores were 7.83±0.488 (knowledge), 6.63±1.7 (practices), and 9.33±1.1 (attitudes). High statistically significant differences were noted between schoolchildren's oral health knowledge, attitudes, and practices before and after implementing the program (p=0.000). There were enhancements in the level of knowledge, with improved positive attitudes and satisfactory practices among schoolchildren after the implementation of the oral hygiene program. Integrating oral hygiene programs into the general curriculum in primary schools and training school nurses, caregivers, and teachers in implementing oral hygiene programs could improve oral health knowledge, attitudes, and practices for preventing oral problems.