© 2019, The Author(s). In this work, we present a comprehensive theoretical and experimental study of quantum confinement in layered platinum diselenide (PtSe2) films as a function of film thickness. Our electrical measurements, in combination with density functional theory calculations, show distinct layer-dependent semimetal-to-semiconductor evolution in PtSe2 films, and highlight the importance of including van der Waals interactions, Green’s function calibration, and screened Coulomb interactions in the determination of the thickness-dependent PtSe2 energy gap. Large-area PtSe2 films of varying thickness (2.5–6.5 nm) were formed at 400 °C by thermally assisted conversion of ultra-thin platinum films on Si/SiO2 substrates. The PtSe2 films exhibit p-type semiconducting behavior with hole mobility values up to 13 cm2/V·s. Metal-oxide-semiconductor field-effect transistors have been fabricated using the grown PtSe2 films and a gate field-controlled switching performance with an ION/IOFF ratio of >230 has been measured at room temperature for a 2.5–3 nm PtSe2 film, while the ratio drops to <2 for 5–6.5 nm-thick PtSe2 films, consistent with a semiconducting-to-semimetallic transition with increasing PtSe2 film thickness. These experimental observations indicate that the low-temperature growth of semimetallic or semiconducting PtSe2 could be integrated into the back-end-of-line of a silicon complementary metal-oxide-semiconductor process.