Indigofera aspalathoides is a medicinal plant with significant traditional importance, known for its anti-inflammatory, antimicrobial, and hepatoprotective properties. In this study, the green synthesis of selenium nanoparticles (SeNPs) was performed using I. aspalathoides ethanolic extract and characterized through Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), x-ray diffraction (XRD), and dynamic light scattering (DLS) analytical techniques. The synthesized SeNPs were evaluated for antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging assays, cytotoxicity using the MTT assay against the MCF-7 breast cancer cell line, and hepatoprotective potential against the HepG2 liver cancer cell line. Characterization confirmed that the SeNPs possessed a stable, spherical structure with an optimal size range of 50-80 nm, enhancing their bioavailability and biological interactions. The SeNPs demonstrated remarkable antioxidant activity, achieving 70.32% DPPH scavenging and 73.68% hydroxyl radical scavenging, significantly surpassing the activity of the plant extract alone. The hepatoprotective effects were dose dependent, with maximum protection of HepG2 liver cells observed at 88 μg/mL (100% viability), but higher concentrations (100 μg/mL) showed some cytotoxicity. These results underscore the potential of I. aspalathoides-derived SeNPs as innovative nanomedicine solutions for addressing oxidative stress, hepatic disorders, and infections.