Diabetes, a non-communicable metabolic disease, causes multiple complications and deaths worldwide. It is a complex, chronic disease that requires continuous medical care with multifactorial risk reduction strategies beyond glycemic control. Ongoing patient education and self-management support are critical for preventing acute complications and reducing the risk of long-term complications. There is ample evidence that healthy lifestyle choices, such as a healthy diet, moderate weight loss, and regular exercise, can maintain normal blood sugar levels and minimize diabetes-related complications. In addition, this lifestyle change has a major impact on controlling hyperglycemia and can help to maintain normal blood sugar levels. This study aimed to assess lifestyle modification and medication use in patients with diabetes mellitus at Jimma University Medical Center. Hospital-based prospective cross-sectional study was conducted from April 1 to September 30, 2021 among DM patients who have follow-up at diabetic clinic of Jimma University Medical Center. Consecutive sampling was used until the required sample size was achieved. Data were checked for completeness, then entered into Epidata version 4.2 software and exported to SPSS version 21.0. Pearson's chi-square test was performed to determine the association between KAP and independent factors. Variables with a p value < 0.05 were considered significant. A total of 190 participants took part in this study with a response rate of 100%. In this study, 69 (36.3%) participants had good knowledge, 82 (43.2%) moderate knowledge and 39 (20.5%) poor knowledge, 153 (85.8%) had positive attitudes, 141 (74.2%) had good practice. Marital status, Occupational status and educational status were significantly associated with knowledge and attitude towards LSM and medication use. Marital status was the only variable that remained significantly associated with knowledge, attitude and practice towards LSM and medication use. The result of this study showed that more than 20% of the participants had poor knowledge, attitude, and practice towards medication use and LSM. Marital status was the only variable which remained to be significantly associated with KAP towards LSM and medication use.