Background <p>Pain is a common health problem and a leading reason for hospital admissions in children. Rational drug use is crucial in pediatric pain management, especially for young children who rely on their parents.</p> Purpose <p>This study aimed to determine the attitudes of mothers of children aged 0–6 years toward rational drug use in pain management.</p> Methods <p>This descriptive, cross-sectional, and correlational study involved 403 mothers attending pediatric outpatient clinics at a university hospital. Data collection took place between April and June 2024 using a personal information form and the Parental Attitude Scale Towards Rational Drug Use (PASRDU). Data analysis included the Mann-Whitney U test for pairwise comparisons, the Kruskal-Wallis H test for groups larger than two, and Spearman Correlation analysis for variable relationships.</p> Results <p>The mean age of the mothers was 31.60 (± 5.328) years; 45.4% had one child, and 50.9% held a university degree or higher. The mean PASRDU score was 174.01 ± 17.225. A statistically significant positive attitude towards rational drug use was linked to younger mothers, those with fewer children, and those with higher education and socioeconomic status (<i>p</i> &lt; .005). PASRDU scores were also higher among mothers who reported greater self-efficacy in relieving their child’s pain and those who did not administer non-prescribed analgesics (<i>p</i> &lt; .005).</p> Conclusions <p>Mothers generally exhibited high attitudes toward rational drug use in pain management. Attitudes varied by age, education, number of children, socioeconomic status, self-perceived competence in pain management, and use of non-prescribed medications. Nurse-led assessment and tailored education may support rational drug use in pediatric pain management.</p> Trial registration <p>Not applicable.</p>