Molybdenum trioxide (MoO<inf>3</inf>) nanoparticles are potential candidates for biomedical applications. In this study, a facile co-precipitation approach using hydrochloric and nitric acids is adopted to synthesize MoO<inf>3</inf> nanoparticles. Further, their antioxidant and antidiabetic potencies were explored. Structure analysis revealed that the synthesized nanoparticles possess a thermodynamically stable orthorhombic phase and that the MoO<inf>3</inf> nanoparticles derived with nitric acid have a smaller crystallite size of 43 nm than the 48 nm size of the nanoparticles derived with hydrochloric acid. Both types of MoO<inf>3</inf> nanoparticles show good thermal stability over a broad range of temperatures. Bandgap studies disclosed that the MoO<inf>3</inf> nanoparticles derived with nitric acid exhibited bandgap shrinkage over the MoO<inf>3</inf> nanoparticles derived with hydrochloric acid. Fourier transform infrared (FTIR) investigations confirmed the orthorhombic phase formation of the as-prepared nanoparticles. Surface morphological exploration revealed clustered grains with smooth surfaces for both types of MoO<inf>3</inf> nanoparticles. MoO<inf>3</inf> nanoparticles derived with nitric acid exhibited greater antioxidant activity in superoxide anion radical (IC<inf>50</inf> value - 114.0.49 ± 0.49 μg/mL) and DPPH (IC<inf>50</inf> value - 121.85 ± 0.96 μg/mL) scavenging assays, and better inhibition of α-glucosidase (IC<inf>50</inf> value - 106.68 ± 1.55 μg/mL) and α-amylase (IC<inf>50</inf> value - 91.77 ± 0.46 μg/mL) enzymes than the nanoparticles derived with hydrochloric acid. The MoO<inf>3</inf> nanoparticles synthesis method, crystallite size, bandgap, and surface morphology make them promising options for developing antidiabetic and antioxidant drugs. © 2025 Elsevier B.V., All rights reserved.