This study demonstrates how chiral liquid chromatography combined with multivariate chemometric techniques, provides a powerful analytical methodology. Although enantiodiscrmination can be possible, the optimization of the analytical procedure to achieve this goal for a given molecule often requires expensive and time - consuming testing of different columns and chromatographic conditions and finally , the most usual scenario is to hardly get baseline resolution but with relatively low enantioseparation factors. Strongly overlapped chromatographic profiles of ofloxacin enantiomers in a sample could be successfully processed and enantiomeric purity could be accurately determined without requiring baseline enantioresolution between peaks by using multivariate chemometric techniques. The samples of ofloxacin were partially enantioseparated with a (R, R) - Whelk- O-2 chiral column under reversed phase condition. Mobile phase was 50 mM potassium dihydrogen phosphate (pH = 2.6) and methanol [60:40, v/v] using 20 μg/ml paracetamol as internal standard. The flow rate was 1.8 ml / min. Signals detected with a diode array detector within a wavelength range from 240 to 260 nm at 5 nm intervals. The developed methods were applied to the quantitative analysis of the investigated enantiomers in tablets. HPLCchemometric techniques using DAD provide reliable results with high sensitivity, accuracy and robustness as well as high peak purity assessment via DAD empowered by PCR and PLS. Chiral HPLC-chemometric combination techniques using stronger mobile phases can elute earlier all interesting peaks and overcome the usual lower enantioresolution factors, therefore, it reduce analysis cost.