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Individuals with disabilities face practical and social challenges beyond those experienced by non-disabled individuals, which may increase vulnerability to mental health problems. However, few studies have examined biochemical correlates of psychological health in this population. This study investigated the associations of serum brain-derived neurotrophic factors (BDNF) and adiponectin with anxiety, depression, and stress among deaf adults. A cross-sectional study was conducted among 204 deaf adults aged 18–45 years. Anxiety and depression were assessed using the DASS-21 questionnaire. Body composition analyses were performed using bioelectrical impedance analysis, and serum BDNF and adiponectin levels were measured. Serum BDNF concentrations were inversely associated with anxiety ( r = −0.632, p < 0.001), depression ( r = −0.732, p < 0.001), and stress ( r = −0.795, p < 0.001). Similarly, serum adiponectin concentrations showed significant inverse correlations with anxiety ( r = −0.422, p < 0.001), depression ( r = −0.344, p < 0.001), and stress ( r = −0.446, p < 0.001). In multiple linear regression analyses adjusted for age, sex, and body mass index (BMI), BDNF remained an independent inverse predictor of anxiety ( β = −0.48, p < 0.001), depression ( β = −0.55, p < 0.001), and stress ( β = −0.62, p < 0.001). Adiponectin also remained independently associated with anxiety ( β = −0.19, p = 0.03) and stress ( β = −0.21, p = 0.02). Lower serum BDNF and adiponectin concentrations were independently associated with higher levels of anxiety, depression, and stress among deaf adults. These findings suggest that BDNF, and to a lesser extent adiponectin, may represent potential biomarkers of psychological distress in this population.