This study aimed to investigate the association between physical activity levels and frailty among patients with diabetes mellitus at Thai Nguyen Hospital A in 2025. A cross-sectional study was conducted on 229 patients diagnosed with type 2 diabetes mellitus according to ADA 2024 criteria. The results showed that the prevalence of frailty and pre-frailty was 27.9% and 41.1%, respectively. The prevalence of individual frailty components was as follows: low handgrip strength (65.8%), slow gait speed (48.7%), poor endurance and energy (39.2%), low physical activity level (35.4%), and unintentional weight loss (23.4%). Univariate and multivariable regression analyses identified low physical activity as the strongest factor associated with frailty. Patients with low physical activity had 6.52 times higher odds of frailty compared to those with activity levels ≥600 MET-minutes/week, with aOR = 6.52 (95% CI: 3.21–13.26), p < 0.001. Other factors independently associated with frailty included older age (per 1-year increase), female sex, and low body mass index (underweight). The findings suggest that routine screening and assessment of physical activity level, nutritional status (body mass index), and frailty using the Fried phenotype should be implemented, and that tailored interventions to increase physical activity (aerobic and resistance training) appropriate to the functional capacity of older adults should be developed and applied to slow the progression of frailty and improve quality of life in patients with type 2 diabetes mellitus.