Background: Most acute respiratory tract infections (ARTIs) in children are due to viral etiology; however, overprescribing of antibiotics for ARTIs is common. Aim: To develop a Stewardship-guided framework for improving antibiotics use among children with ARTIs. Design: A quasi- experimental design (pre-posttest) was utilized for this study. Setting: The Pediatric ward and the pediatric outpatient clinic in Menoufia University Hospital. Sampling: A convenient sample of 43 nurses and a purposive sample of 200 children and their parents were included. Instruments: Five instruments were utilized to get the data. I: Nurses structured interview questionnaire sheet. II: Observational checklist for nurses' antibiotic Stewardship activities. III: Children structured interview questionnaire sheet (children 9-11 years). IV: Children structured interview questionnaire sheet (children 12-15 years). V: Parents structured interview questionnaire sheet. Results: There was a significant improvement in nurses' knowledge and antibiotic Stewardship activities. There was a significant improvement in children' knowledge, beliefs and attitudes regarding antibiotic use. There was a significant decrease in parents' false knowledge/ information, negative attitude and practices regarding antibiotic use after implementation of the Stewardship-guided framework compared to preintervention.  Conclusion: The Stewardship-guided framework was more successful on the posttest than on the pretest in improving nurses' knowledge and antibiotic stewardship activities as well as children' knowledge, beliefs and attitudes regarding antibiotic use, and parents' knowledge, attitudes and practices regarding antibiotic use. Recommendation: Nurses in collaboration with the health care team should integrate the Stewardship-guided framework in all pediatric units and outpatient clinics for improving antibiotic use among pediatric patients.