Introduction: Diabetes mellitus is a major public health problem worldwide, and the prevalence of diabetes mellites is steadily increasing in developing countries including Ethiopia. Adherence to diabetes self-care activities is a vital strategy for the reduction in diabetes mellitus. This study aimed to assess the level of self-care practice and its associated factors among adult diabetes patients in Tercha Zonal diabetes center: A Southern Nation Nationality of Ethiopia. Methods: An facility-based cross-sectional study was conducted among 213 diabetes mellitus patients follow-up at Tercha Zonal diabetes center selected by systematic random sampling. Data were entered into Epi-Data version 4.6 and exported to SPSS version 25 for analysis. Both descriptive and inferential statistics were used to describe and test the association between selected variables. Statistical significance was declared at p-value <0.05. Results: Out of the 213 study participants, only 84 (39.4%) had good self-care practices. The multivariate logistic regression analysis revealed that attending secondary education (AOR=16.015,(95%CI:1.925-133.251),P=0.01] and college and above [AOR=89.553, (95%CI:9.732–824.021),P<0.001]and having diabetes complications [AOR=0.412, (95%CI:0.204 – 0.832), P=0.013] were significantly associated with good self-care practice. Conclusion: The study revealed that a significant number of the study participant have poor self-care practices in the prevention and control of diabetes mellitus. Educational level, and having diabetes complications were found statistically significantly associated with a good level of self-care practice. Therefore, all frontline healthcare providers should provide basic information and counseling regarding diabetes self-care practice.