Herein, we report an eco-friendly, facile, one-pot, green synthesis of nanoceria for multiple biomedical applications. In the study, cerium oxide nanoparticles (CeO-NPs) were synthesized using a simple aqueous extract of as an effective reducing and capping agent. The biosynthesized nanoparticles were characterized UV-vis spectroscopy, X-ray powder diffraction (XRD), high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Raman spectroscopy. The NPs were highly stable, exhibited high purity, and had a spherical morphology and mean size of 28 nm. FTIR and HPLC studies confirmed the successful capping of bioactive compounds on the nanoparticles. The well-characterized NPs were evaluated for a number of biomedical applications, and their antimicrobial (antifungal, antibacterial, and antileishmanial), protein kinase inhibition, anticancer, antioxidant, anti-diabetic and biocompatibility properties were studied. Our results showed that the mediated CeO-NPs were highly active against fungal strains, compared to the tested bacterial strains, with resulting in the largest zone of inhibition (15.1 ± 0.27 mm). The particles also exhibited dose dependent leishmanicidal activity with significant LC values toward both the amastigote (114 μg mL) and promastigote (97 μg mL) forms of the parasite (KWH23). The NPs were found to be moderately active against the HepG2 cell line, showing 26.78% ± 1.16% inhibition at 200 μg mL. Last but not least, their highly biocompatible nature was observed with respect to freshly isolated human red blood cells (hRBCs), making the greenly synthesized CeO-NPs a novel candidates for multidimensional medical applications.