Acrylamide (AA, C₃H₅NO) is a toxic food contaminant formed during high-temperature cooking, posing neurotoxic and carcinogenic risks. Efficient removal and detection of AA are essential for food safety. This study employs density functional theory (DFT) at the B3LYP/6-31G* level to investigate the adsorption of AA on X₁₂Y₁₂ nanocages (X = B, Al; Y = N, P), including B₁₂N₁₂, B₁₂P₁₂, Al₁₂N₁₂, and Al₁₂P₁₂, assessing their potential as adsorbents and electrochemical sensors. Optimized structures indicate the strongest interaction occurs with Al₁₂P₁₂, forming two covalent bonds with an adsorption energy of –227.549 kJ/mol, confirming chemisorption. Al₁₂N₁₂ and B₁₂N₁₂ exhibited moderate adsorption energies of –14.358 kJ/mol and –55.342 kJ/mol, respectively, suggesting mixed physisorption–chemisorption, while B₁₂P₁₂ displayed weak and non-spontaneous adsorption (81.735 kJ/mol). NBO analysis revealed maximal charge transfer (0.15–0.22 e) and stabilization energy (5.0–9.2 kcal/mol) for Al₁₂P₁₂, with minimal transfer for B₁₂P₁₂ (0.02–0.04 e). Thermodynamic results confirmed exothermic and spontaneous adsorption for S1, S2, and S4 complexes (ΔHad < 0, ΔGad < 0), with stronger binding at lower temperatures. FMO and DOS analyses showed bandgap reductions of 43.657% (B₁₂N₁₂) and 25.245% (Al₁₂N₁₂), enhancing electronic conductivity for sensing, whereas Al₁₂P₁₂ showed a moderate 14.047% reduction, reflecting strong adsorption but limited sensor reusability. In conclusion, adsorption strength increases from B₁₂P₁₂ < B₁₂N₁₂ < Al₁₂N₁₂ < Al₁₂P₁₂, while physisorption decreases. Al₁₂P₁₂ is the most promising adsorbent for AA removal, and B₁₂N₁₂ and Al₁₂N₁₂ are suitable for electrochemical sensing, providing quantitative guidance for designing nanostructured materials in food safety applications.