In this work, the active ingredients of Entacapone, Levodopa and Carbidopa in drug samples used in the treatment of Parkinson's disease were quantitatively determined by Ultraviolet Visible (UV-VIS) Spectroscopy and chemometrics. Firstly, the spectra of each drug active ingredient were taken individually and then synthetic mixtures identical to the drug sample were analyzed. In our method, validation parameters were calculated for each method. Percent (%) recoveries were found on average for both the synthetic mixture and the commercial sample. The recoveries were quantitative for each method. The accuracy of the methods was tested by applying ANOVA test to the results obtained from the PLS and PCR calibration methods. The developed methods are reproducible, sensitive, and accurate, and can be recommended for the analysis of drug samples containing Entacapone, Levodopa, and Carbidopa