Diabetes Empowerment is important for diabetic control as it postpones the onset of complications. This study aimed to investigate the association of medication adherence, self-care behaviors, and diabetes knowledge with Diabetes Empowerment among patients with type II diabetes. A cross-sectional study was conducted on 451 type II diabetes patients attending Endocrinology clinics at OPD setting in Karachi. Data was collected electronically using a structured questionnaire comprising of tools to measure Diabetes Empowerment, medication adherence, self-care behaviors, diabetes knowledge, and socioeconomic scale. It also included health-related information from patients’ medical record. As outcome variable was continuous, so multiple linear regression analysis was used to assess the independent effect of Diabetes Empowerment on medication adherence, self-care behaviors and diabetes knowledge with other co-variates. The mean Diabetes Empowerment score was 3.62 (SD = 0.31). The mean age of the participants was 56.68 (SD = 11.76). 53.88% were females, 80.71% were married, 77.56% were obese, and 66.30% were upper-middle class with average diabetes duration of 11.7 years (SD = 7.89). HbA1c values were ≥ 7 in 63.41% of study participants. Diabetes Empowerment was significantly associated with medication adherence (P = 0.001), general diet (P < 0.001), special diet (P = 0.011), smoking status (P = 0.001), and socioeconomic status (upper lower, P = 0.085). A comprehensive strategy for the treatment of type II diabetes is essential to enhance clinical results, improve patient quality of life, and prevent diabetes-related comorbidities. People with type II diabetes should be encouraged to embrace an empowerment-based approach by healthcare providers. It is critical to do research that promotes empowerment.