Attesting optimal drug concentrations in biological fluids is crucial to ensure precise dosage adjustment, to guarantee therapy adherence, and to manage side effects in chemotherapy. Accurate drug determination relies on liquid chromatography and advanced detectors, with sample preparation playing a pivotal role, especially in complex matrices such as biological fluids. This study introduces a multiphase electroextraction (MPEE) of doxorubicin (DOX) in saliva by utilizing a paper point, followed by ultra‐high‐performance liquid chromatography coupled to diode array detection. The extraction time and electric potential were carried out by using the Doehlert optimization approach, whereas the desorption solvent was fine‐tuned through the centroid–simplex experimental design. After optimization, DOX and the internal standard were extracted in 35 min, utilizing an applied voltage of 300 V and a multiwell plate capable of simultaneous extraction of 66 samples. The recovery was 87%–101%, with a linear range between 50 and 500 µg L−1 (R2 > 0.999). The intra‐ and inter‐assay coefficients of variation for precision were <10%, and the limit of detection and limit of quantification were 25 and 50 µg L−¹, respectively. When applied to five different fortified saliva samples, there were no statistically significant differences in the detected concentrations. Although the enrichment factor (0.6) was not as high as expected, the other results confirm that the method obtained is suitable for monitoring DOX in this complex matrix and can contribute to further developments in sample preparation using MPEE approaches.