Background: Carpal tunnel syndrome is the most prevalent peripheral nerve entrapment condition of the upper limb. Among metabolic risk factors, diabetes is considered the most relevant. Although wrist ultrasound assessment of the median nerve has demonstrated a good correlation with the gold standard for the diagnosis of this syndrome, neurophysiological study, its usefulness in patients with diabetes is questionable because the compressive phenomenon is not the predominant one. Method: We conducted a retrospective study to compare the clinical and median nerve ultrasound features of patients with carpal tunnel syndrome previously diagnosed or not diagnosed with diabetes. Additionally, a linear multivariate regression analysis was performed to determine to what extent the cross-sectional area of the median nerve was dependent on the condition of diabetes by fixing other variables such as sex, age, or time of evolution. Results: We included 303 records of patients (mean age 44.3 ± 11.7 years old, 57.89% female, mean of time of evolution 13.6 ± 8.3 months) from 2012 to 2020. The cross-sectional area of the median nerve was 10.46 ± 1.44 mm2 in non-diabetic patients and 8.92 ± 0.9 mm2 in diabetic patients (p < 0.001). Additionally, diabetic patients had a shorter time of evolution (7.91 ± 8.28 months vs. 14.36 ± 0.526 months, p < 0.001). In the multivariate analysis, the resultant model (fixed R-square = 0.659, p = 0.003) included a constant of the following four variables: the evolution time (Beta coeff. = 0.108, p < 0.001 95% CI 0.091 to 0.126, standardized coeff. = 0.611), the condition of diabetes (Beta coeff. = −0.623, p < 0.001 95% CI −0.907 to −0.339, standardized coeff. = −0.152), the severity (Beta coeff. = 0.359, p = 0.001 95% CI 0.147 to 0.571, standardized coeff. = 0.169), and the masculine sex (Beta coeff. = 0.309, p = 0.003, 95% CI 0.109 to 0.509, standardized coeff. = 0.103). Conclusions: Ultrasound assessment of the median nerve in patients with diabetes is not a useful tool to confirm whether carpal tunnel syndrome should be diagnosed or not diagnosed.