Background <p>Type 2 diabetes mellitus (T2DM) is a growing global health burden often accompanied by multiple comorbidities that complicate management and worsen clinical outcomes. Understanding the epidemiological profile of these comorbid conditions is essential for developing integrated and effective diabetes care strategies, particularly in low- and middle-income countries such as Nepal. This study aimed to determine the prevalence and factors associated with common comorbidities among patients with T2DM in Nepal.</p> Methods <p>This was a cross-sectional household study. The primary data was collected from T2DM patients in Madhesh Province, Nepal. Multistage sampling was used to select 492 patients with T2DM from the population. Data was collected through structured interviews, and comorbidities were documented based on patients self-reports and subsequently verified with physician prescriptions. Data on demographic characteristics, clinical profiles, and behaviour and lifestyle factors were collected as potential predictors of comorbidities. Descriptive statistics and logistic regression were employed to determine the prevalence and associated factors of comorbidities.</p> Results <p>Among 492 patients with T2DM, 92.1% had at least one comorbidity. The most common comorbidity was nephropathy (40.1%), followed by hypertension (25.4%), cardiac problems (21.1%), retinopathy (18.5%), and neuropathy (9.8%). Logistic regression model demonstrated that males had higher odds of hypertension (AOR = 1.734; 95% CI: 1.077–2.791), while poor diet adherence increased the risk of hypertension (AOR = 2.04; 95% CI: 1.195–3.481). Cardiac comorbidities were associated with lower education (primary: AOR = 3.743; 95% CI: 1.696–8.258; secondary: 2.986; 95% CI: 1.455–6.129) and were less common among individuals engaged in business professions (AOR = 0.351; 95% CI: 0.139–0.887). Nephropathy was strongly associated with uncontrolled glycemia (AOR = 2.220; 95% CI: 1.378–3.577) and with comparatively younger age (35–50 years) (AOR = 14.292; 95% CI: 6.36–32.19). Retinopathy risk decreased with dietary compliance (AOR = 0.525; 95% CI: 0.297–0.828), and food avoidance (AOR = 0.607; 95% CI: 0.385– 0.957).</p> Conclusion <p>This study highlights a substantial burden of both microvascular and macrovascular comorbidities among patients with T2DM, with nephropathy being the most prevalent. Prioritize integrated care for diabetes and its related comorbidities with targeted support for age-specific patients, those with poor glycemic control, lower educational levels, longer disease duration, and poor dietary adherence.</p>