The study assessed nutritional knowledge and dietary compliance of type 2 diabetes mellitus (T2DM) patients in the context of diabetes self-care, and the association between nutritional knowledge and dietary compliance. A report from a recent population-based study indicates that between 3.3% and 6% of Ghanaian adults are living with diabetes mellitus (DM) and this is projected to reach 820,000 by 2035. Diet therapy and self-care form an integral part of T2DM management, however, little is known about the nutritional knowledge and dietary habit of DM patients accessing healthcare at the Bono Regional Hospital in Ghana. This study sought to fill the existing knowledge gap which is critical to addressing the challenges associated with the management of T2DM. A hospital-based, descriptive cross-sectional study design was employed to assess nutritional knowledge and dietary compliance of T2DM patients in the context of diabetes self-care, and the association between them. The study was carried out at the Bono Regional Hospital in Sunyani, Ghana. Respondents were recruited using systematic sampling and semi-structured, interview-administered questionnaires were used to collect data for the study. The primary data for the study were analyzed using Statistical Package for Social Sciences (SPSS) version 25. A total of 140 T2DM patients responded to our questionnaires. The majority of the respondents (98.6%) were above 35 years of age. Females constituted 66.4% of the total sample. About one-third of the respondents were farmers (36.4%). Based on our specified criteria, the majority of respondents (52.1%) demonstrated good nutritional knowledge, however, only 39.3% of them showed good dietary compliance. A Pearson’s chi-square test (with Yates’ Continuity Correction) showed a statistically significant association between nutritional knowledge and overall dietary compliance, χ2 (1, n = 140) = 10.23, P = .001, phi = .27. Also, nutritional knowledge was associated with consumption of complex carbohydrates χ2 (1, n = 140) = 7.43, P = .009, phi = -.23, low-fat diet χ2 (1, n = 140) = 8.51, P = .005, phi = -.274, and controlled portions of proteins χ2 (1, n = 140) = 10.67, P = .002, phi = .24. Dietary compliance was poor despite good nutritional knowledge. However, there was a significant association between good nutritional knowledge and overall dietary compliance. Therefore, comprehensive nutritional education, tailored to patients’ needs, and socio-cultural and economic situations could help to promote adherence to dietary recommendations among T2DM patients accessing healthcare at the Bono Regional Hospital.