Objective Depressive symptoms are common among older adults with obesity and diabetes. Nonetheless, the mechanisms for this association are not clear but may involve changes in the insulin cascade signaling. We aimed to investigate the association, and potential mediators, between obesity, insulin resistance, and depressive symptoms among older adults from a homogenous cohort of Mexican‐Americans. Methods We included a total of 500 Mexican‐American older adults assessed in the Cameron County Health Study. We evaluated depressive symptoms using the Center for Epidemiologic Survey Depression Scale (CES‐D). Central obesity was defined by waist circumference. Insulin resistance was evaluated by the HOMA‐IR index. We estimated the association between obesity, insulin resistance, and depressive symptoms by carrying out univariate and multivariate regression analyses. Results In unadjusted regression analysis, HOMA‐IR (unstandardized β = 0.31 ± 0.12, P = 0.007), waist circumference (unstandardized β = 0.066 ± 0.0.028, P = 0.017), and Hb1Ac levels (unstandardized β = 0.52 ± 0.24, P = 0.03) were significantly associated with CES‐D scores. The association of HOMA‐IR and CES‐D remained statistically significant after controlling for socio‐demographic and clinical variables in multivariate analysis (unstandardized β = 0.28 ± 0.11, P = 0.01). Conclusion Our results suggest that depressive symptoms are associated with insulin resistance in older Mexican‐American adults. In addition, poorer glucose control and obesity are important mediators of this relationship. Additional studies are needed to evaluate whether interventions that increase insulin sensitivity can also reduce depressive symptoms in this population. Key points Depression is very common among older Mexican‐American population. Cardiometabolic disorders are common comorbidities in depression, and these conditions may share common pathophysiological mechanisms. Our findings provide further support to the role of insulin resistance as a mechanism linking depression and cardiometabolic disorders in the elderly.