This study describes the preparation of poly(methyl methacrylate) (PMMA) composites reinforced with various loadings (0 wt.%, 1.2 wt.%, 2.4 wt.%, and 3.6 wt.%) of indium oxide (In 2 O 3 ) using solution casting. Fourier-transformation infrared spectroscopy was used to analyze the structural characteristics of the nanocomposite and confirm the physical interactions between In 2 O 3 nanoparticles (NPs) and the PMMA matrix. Field emission scanning electron microscopy was used to examine the nanocomposite surface and showed that the In 2 O 3 NPs were distributed and homogenous through the PMMA matrix. An increase in the ratio of In 2 O 3 NPs in the PMMA changed the optical characteristics with an increase in the absorbance, absorption coefficient, refractive index, extinction coefficient, and real and imaginary dielectric constants and a decrease in the transmittance and indirect energy gap. The absorption coefficient was < 10 4 cm −1 , confirming the indirect electron transition. The antibacterial effect of PMMA/In 2 O 3 films were examined against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli and demonstrated an increase in inhibition zone diameter with an increase in In 2 O 3 NP content. Thus, the PMMA/In 2 O 3 nanocomposite exhibited antibacterial activity.