Display omitted •Bio-safe ligand-free and easily dispersible ZnO QDs were prepared by a novel organometallic strategy.•The process involves transformation of a DMSO solution of Et2Zn upon air exposition.•DMSO acts both as a solvent and a low-molecular-weight l-type surface protector.•The resulting QDs display unique long-term colloidal stability.•The developed method leads to the rational-by-design ZnO-based functional materials. Colloidal quantum dots (QDs) are of widespread importance for their unique combination of physicochemical properties and a number of prospective applications, and the search for efficient synthetic methods to produce readily dispersible, functionally stable and ligand-free quantum dot-based inks is a vital and timely area of research. We describe a convenient room-temperature and non-external-surfactant-assisted organometallic synthetic strategy for the reproducible preparation of solution-processable organic ligand-free zinc oxide (ZnO) QDs. The process involves the controlled transformation of a DMSO solution of commercially available diethylzinc upon exposition towards atmospheric air, where H2O and O2 act simultaneously as oxygen sources, and DMSO acts both as a solvent and a low-molecular-weight l-type surface protector. The resulting QDs with a narrow size distribution (4.7 ± 0.8 nm) were comprehensively characterized with a combination of various analytical techniques, which nicely documented their unique stabilities when dried, precipitated, re-dissolved or exposed to air. Moreover, to substantiate idealized surface passivation of the resulting QDs, we investigated their stability in the biological environment and nano-specific activity toward selected normal and cancer cell lines, and no significant toxic effect was revealed. Undoubtedly, the reported one-step-one-pot organometallic approach paves the way to high-quality and bio-stable ZnO QDs coated by an easily and reversibly removable organic shell, auguring applications in a vast array of devices and nanomedicine.