Diarrheal disease is the second leading cause of death worldwide in children under 5 years old, after pneumonia. Fortunately, diarrhea is a preventable disease that can be avoided by implementing basic home management strategies. Mothers are essential to its management and prevention; therefore, this study assessed the knowledge, attitudes, and practices of mothers in Pakistan related to diarrheal disease prevention and management. The study was conducted using a cross-sectional design in three cities of Pakistan from September 2022 to December 2022. A questionnaire was used to collect data on mothers' sociodemographic characteristics and their knowledge, attitudes, and practices related to the prevention and management of diarrheal diseases. A total of 356 mothers (81.7% of them were housewives, and 58.4% were 25-34 years old) participated in the study. Data were analyzed using descriptive statistics and tests of association. Significant associations were found between mothers' income, education, and ethnicity and their knowledge, attitudes, and practices regarding the prevention and management of diarrheal diseases (P <0.05). However, no significant association was found between the other variables. The knowledge and attitudes of the mothers regarding the prevention and management of diarrhea were satisfactory; however, their prevention-related practices and home-based management were unsatisfactory. Therefore, community education, formation of health and hygiene committees, and dissemination of user-friendly information are crucial for creating awareness about the prevention and management of diarrheal diseases. These measures can help improve the practices of mothers and reduce the incidence of diarrheal diseases in Pakistan.