Background: Nocturnal enuresis is a prevalent and emotionally challenging condition that has a significant impact on psychological, emotional, and social consequences for both the child and their family.  Aim: to evaluate the designed nursing program on mothers' knowledge, practices and its effect on their children with nocturnal enuresis. Subject and Method: Quasi-experimental research design (pre – post program) was utilized in current study. The study was conducted at the Pediatric Outpatient Nephrology and Urology clinic at Minia University Hospital. A purposive sample of 60 mothers of children with Nocturnal Enuresis. Three tools were used in study, tool(I) structured interview questionnaire, tool(II) mothers self-reported practices regarding nocturnal enuresis and tool(III) effect of nocturnal enuresis on children. Data was collected over 7 months from the beginning of June 2023 to December 2023. Results: One-third of the mothers aged 30-40, with a mean 33.3 ± 7.6 years, have secondary education, three-quarters of them are housewives, and live in rural areas. Regarding the level of mothers' knowledge, more than two-thirds of them had unsatisfactory levels regarding nocturnal enuresis before the training program; however, this decreased to none after three months with a highly significant difference. Before the program, the majority of mothers reported unsatisfactory nocturnal enuresis practices, which dropped to none after three months with substantial statistical significance. Conclusion: A designed nursing program effectively enhances mothers' knowledge practices and has a positive effect on their children with nocturnal enuresis. Recommendations: Implement ongoing educational programs for mothers to maintain and further improve their knowledge and practices regarding nocturnal enuresis.