For the first time, we applied cell-population based mass spectrometry (CP-MS) for biosensing intact eukaryotic cells of Chlamydomonas reinhardtii and Saccharomyces cerevisiae. Cell counts ranging from 1×10 7 to 1.28×10 2 were analyzed using MALDI-MS to obtain the threshold detection sensitivity. Platinum nanodots (Pt NDs) were used to enhance the detection sensitivity of CP-MS. Pt NDs were able to improve the detection sensitivity of CP-MS from 3200cells/mL to 640cells/mL (5-fold) for Chlamydomonas. For yeast cells, the detection sensitivity was also increased from 400,000cells/mL to 3200cells/mL (125-fold) when Pt NDs were used. Using the Clin Pro tool, the obtained results from MALDI-MS data were validated. Statistical analysis of the mass data was performed using MYSTAT software.