Amino acid-modified carbon interfaces have huge applications in developing electrochemical sensing applications. Earlier reports suggested that the amine group of amino acids acted as an oxidation center at the amino acid-modified electrode interface. It was interesting to locate the oxidation centers of amino acids in the presence of guanidine. In the present work, we modeled the arginine-modified carbon interface and utilized frontier molecular orbitals and analytical Fukui functions based on the first principle study computations to analyze arginine-modified CPE (AMCPE) at a molecular level. The frontier molecular orbital and analytical Fukui results suggest that the guanidine (oxidation) and carboxylic acid (reduction) groups of arginine act as additional electron transfer sites on the AMCPE surface. To support the theoretical observations, we prepared the arginine-modified CPE (AMCPE) for the cyclic voltammetric sensing of dopamine (DA). The AMCPE showed excellent performance in detecting DA in blood serum samples.