This study characterizes a newly developed simple, rapid, sensitive and cost effective spectrophotometric method for the microdetermination of Methyldopa and Etilefrine hydrochloride in pure form and pharmaceutical formulations. The developed method is based on the reaction of copper (II) with studied drugs in the presence of neocuproine (NC) (2,9-dimethyl-1,10-phenanthroline) reagent. Copper (II) is reduced easily by both drugs to Cu (I)–neocuproine chelate, which shows an absorption maximum at 455 nm. Results showed that percentage recoveries for the suggested method were 99.822 ± 0.797 and 100.027 ± 0.469 within the concentration ranges of 0.4-3.6 and 1.2-6.8 μg/mL with a minimum detection limit (LOD) of 0.115 and 0.348 μg/mL and a quantification limit (LOQ) of 0.348 and 1.086 μg/mL for Methyldopa and Etilefrine hydrochloride respectively. The suggested method was applied successfully for determination of both drugs in pure form and pharmaceutical formulations without interference of common pharmaceutical excipients or additives with the assay results.