Orthorhombic SrIrO3 is a correlated metal whose electronic properties are highly susceptible to external perturbations due to the comparable interactions of spin–orbit interaction and electronic correlation. We have investigated the electronic properties of epitaxial orthorhombic SrIrO3 thin-films under compressive strain using transport measurements, optical absorption spectra, and magnetoresistance. The metastable, orthorhombic SrIrO3 thin-films are synthesized on various substrates using an epi-stabilization technique. We have observed that as in-plane lattice compression is increased, the dc-resistivity (ρ) of the thin films increases by a few orders of magnitude, and the dρ/dT changes from positive to negative values. However, optical absorption spectra show Drude-like, metallic responses without an optical gap opening for all compressively strained thin films. Transport measurements under magnetic fields show negative magnetoresistance at low temperature for compressively strained thin-films. Our results suggest that weak localization is responsible for the strain-induced metal–insulator transition for the orthorhombic SrIrO3 thin-films.