Background: Food insecurity (FI), which is defined as limited or uncertain access to sufficient, nutritious food, disproportionately affects low-income populations and has been linked to poor control of chronic diseases including type 2 diabetes mellitus (T2DM) with North Louisiana having one of the highest rates of FI in the United States. The interaction between FI and neighborhood-level socioeconomic disadvantage has not been well characterized in relation to microvascular diabetic complications. Objective: This study aimed to evaluate the relationship between FI, socioeconomic disadvantage, and microvascular complications in patients with T2DM. Methods: A retrospective cohort study of 163 adult patients with T2DM who received care at Ochsner LSU Health clinics in Shreveport and Monroe, Louisiana, between January 2018 and January 2023 were reviewed. FI status, Area Deprivation Index (ADI), a validated measure on neighborhood socioeconomic disadvantage, and microvascular complication outcomes including nephropathy, neuropathy, and retinopathy were obtained from electronic medical records. FI was assessed using the validated two-item Hunger Vital Sign screening tool. Results: The study found that FI alone was not a statistically significant predictor of nephropathy based on microalbumin-to-creatinine ratio (MACR). However, the combination of FI and high ADI (≥7) was significantly associated with neuropathy (p = 0.024) and retinopathy (p < 0.001), particularly among patients with T2DM for more than five years. Additionally, the interaction between FI and high ADI was also found to influence MACR values significantly (p = 0.026), indicating that socioeconomic stressors may exacerbate kidney dysfunction. Conclusions: Food insecurity, coupled with socioeconomic adversity, was associated with an increased risk of microvascular complications in T2DM. These results highlight the importance of integrating FI screening and addressing social determinants of health in high-risk populations. Early identification and targeted interventions could help mitigate disease progression and reduce health disparities.