BackgroundGestational diabetes mellitus (GDM) is a chronic condition characterized by glucose intolerance during pregnancy and is particularly common in low- and middle-income countries, where it poses significant health risks to both mothers and their fetuses. Research on this topic in Ethiopia has been limited, especially regarding the World Health Organization’s 2013 guidelines for universal screening. This study aims to evaluate the prevalence of GDM and identify its influencing factors among women attending antenatal clinics in the Sidama regional state. MethodsA cross-sectional study in the Sidama Region included 685 pregnant women who underwent a two-hour Oral Glucose Tolerance Test for universal screening and diagnosis of gestational diabetes mellitus (GDM). The prevalence of GDM was evaluated using descriptive statistics and multivariate analysis with the adjusted odds ratio (AOR) at a 95% confidence interval and a significance level of 0.05. ResultsThe study, comprising 685 participants, attained a 92.4 % response rate, indicating a 16.1 % prevalence of GDM overall and an average post-glucose load level of 0.99 mmole/L. Factors such as living in urban areas (AOR = 1.69, 95 % CI (1.011, 2.82)), being widowed (AOR = 2.23,95 % CI (1.00,5.08)), history of previous abortions (AOR = 2.59,95 %CI(1.50,4.50)), prior caesarean section(AOR = 0.14,95 % CI (0.07,0.27)), gravidity (AOR = 0.77,95 % CI (0.64,0.94)), parity (AOR = 1.93, 95 % CI (1.54, 2.42)), and HIV/AIDS status (AOR = 4.06, 95 % CI (2.18, 7.58)) were independently associated with GDM. ConclusionThe study revealed a gestational diabetes mellitus (GDM) prevalence of 16.1% in the Sidama region of Ethiopia, consistent with findings from other recent studies across the country. It also identified several key independent risk factors for GDM, including urban residency, widowhood, prior abortions or cesarean deliveries, HIV status, gravidity, and parity. The results emphasize the critical need for targeted interventions and continuous monitoring of GDM among pregnant women, particularly in regions with high prevalence. To enhance maternal health outcomes in Ethiopia and beyond, it is crucial to incorporate these findings into comprehensive healthcare strategies.