Aims: Self-monitoring of blood glucose can improve treatment adherence and clinical outcomes. The aim of this study is to assess knowledge, practice, and barriers to self-monitoring of blood glucose (SMBG) among patients with type 2 diabetes mellitus (T2DM) in Enugu State, Nigeria. Settings and Design: This study was a cross-sectional survey of 340 patients with type 2 diabetes at the University of Nigeria Teaching Hospital (UNTH) and Enugu State University Teaching Hospital (Park Lane) in August 2017. Materials and Methods: The data collection tool was a 26-item, four-sectioned questionnaire: the socio-demographic and clinical characteristics, 11 items on knowledge, seven on practice, and eight on barriers regarding SMBG. The questionnaires were self-administered. Statistical Analysis Used: Data were analyzed using SPSS version 20. Descriptive, χ2, Spearman's correlation, and logistics regression statistics were reported at P < 0.05. Results: Majority of the patients were 46–55 years old (27.9%). Female respondents were 53.5%. Patients with good knowledge and practice were 35.9% and 46.2%, respectively. Knowledge of SMBG was negatively correlated to barrier against SMBG (r = -0.178, P=0.001) and positively correlated with practice of SMBG (r = 0.138, P=0.011). Those who were not taught SMBG were less likely to have good practice of SMBG than those who were taught (adjusted odd ratio 0.122, 95% confidence interval: 0.044–0.338). Conclusions: Patients with T2DM in Enugu State have poor knowledge and practice SMBG.