Objective The prevalence of type 2 diabetes mellitus (T2DM) in Vietnam has doubled from 3% to 6% over the last decades, with potential consequences for persons with diabetes and their caregivers. This study aimed to assess caregiver burdens and factors associated with caregiver burden. Method A cross-sectional study was conducted in 2019, using data from 1,241 informal caregivers (ICGs). Caregiver burden was scored from 0–32 using 8 questions from the Zarit Burden Interview (ZBI). Quantile regression analysis was used to identify factors associated with caregiver burden. Results The median score of the ZBI was 7.0 (Q1-Q3: 2.0–10.0), indicating that the burden among caregiver of persons with T2DM is not high. Quantile regression showed that the higher the monthly income, the lower the burden among caregivers (50% quantile and 75% quantile of burden: -0.004). Lower educational level (25%Q: 4.0, 50%Q; 3.0, 75%Q: 2.16), being a farmer (25%Q: 2.0) and providing care to other people besides the person with T2DM (25%Q: 2.0, 50%Q; 2.54, 75%Q: 1.66) were associated with higher burden on caregivers. Conclusion The study found that caregivers facing additional life stressors, such as low income or other caregiving responsibilities, reported higher levels of burden. These findings could inform the development of interventions targeted at supporting informal caregivers in rural areas in low- and middle-income countries.