This study reports the green synthesis of Yttria-Zinc Oxide (Y2O3 - ZnO) (YOZ) nanohybrids using Caulerpa lentillifera extract as a green stabilizer and evaluates the effect of pH variation (9.0, 10.0, 11.0) on their physicochemical and biomedical properties. Sol-gel-hydrothermal synthesis followed by calcination at 600 °C produced YOZ nanohybrids (YOZ-9, YOZ-10, YOZ-11), with ZnO and Y₂O₃ used as comparative controls. The XRD patterns of YOZ confirmed the coexistence of hexagonal wurtzite ZnO and cubic Y2O3, with emphasis on the dominant (101) plane, which exhibited the highest crystallinity intensity. The crystallite size ranged from 41.8 to 48.1 nm. Meanwhile, the FTIR spectra revealed Zn-O-Y vibrations (400–600 cm−1), supported by biomolecular residues that indicated successful hybridization. Thermal analysis showed improved stability up to ∼850 °C, and UV–Vis DRS demonstrated a narrowed bandgap (3.09–3.07 eV) compared with ZnO (3.17 eV). The SEM images showed distinct morphologies at each pH, with highly uniform nanorods observed at YOZ-11. YOZ-11 exhibited the highest antibacterial activity against Staphylococcus aureus (25 mm, MIC: 184.09 μg/mL) and Candida albicans (23 mm, MIC: 159.66 μg/mL). Each of the other biomedical parameters also showed stronger indications than the positive controls, including along with strong of antioxidant activity (IC50 = 43.77 μg/mL), anti-inflammatory activity (59.78 μg/L), antidiabetic activity (429.90 μg/mL). These findings highlight the Caulerpa lentillifera based YOZ nanohybrids as stable, eco-friendly, and multifunctional materials showing promising photoresponsive multifunctional biomedical activity under controlled irradiation conditions. © 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.