Background <p>Hypoglycemia is a medical emergency that causes hospital admission and emergency department visits. Knowledge of hypoglycemia prevention is essential because a knowledgeable patient is more likely to practice hypoglycemia prevention. Despite this fact, the knowledge and practice of hypoglycemia prevention and its associated factors among patients with diabetes have been insufficiently studied in Oromia.</p> Objective <p>To assess knowledge and practice of hypoglycemia prevention and its associated factors among patients with diabetes in West Shewa, Ethiopia, 2023.</p> Methods <p>Cross-sectional study design conducted from May 01 to June 01, 2023. A systematic random sampling technique was used to select 393 participants with proportional allocation. A pre-tested, structured, and interviewer-administered questionnaire was used to collect data. The data was entered using EpiData version 4.6 and then exported to SPSS software version 25 for further processing. A binary logistic regression model was performed to determine the association between the dependent and independent variables. Factors with <i>p</i>-value &lt; 0.25 on bivariate analysis were taken to the multivariate analysis. The strength of association is determined by AOR. The level of significance is declared at <i>p</i>-value &lt; 0.05 with 95% CI.</p> Result <p>Among the total respondents, 273(70.9%) live with Type2 DM and 131(34.0%) used insulin. Generally, 59.7% and 47% of respondents had good knowledge and practice of hypoglycemia prevention, respectively. The educational level, using insulin, and monthly income were associated with good knowledge. Whereas educational level, having a glucometer, and knowledge were associated with good practice of hypoglycemia prevention.</p> Conclusion <p>The study shows there is a knowledge and practice gap regarding hypoglycemia prevention.</p>