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ABSTRACT Reticulum II (Ret II) is a satellite galaxy of the Milky Way (MW) and presents a prime target to investigate the nature of dark matter (DM) because of its high mass-to-light ratio. We evaluate a dedicated INTEGRAL observation campaign data set to obtain γ-ray fluxes from Ret II and compare those with expectations from DM. Ret II is not detected in the γ-ray band 25–8000 keV, and we derive a flux limit of ${\lesssim}10^{-8}\, \mathrm{erg\, cm^{-2}\, s^{-1}}$. The previously reported 511 keV line is not seen, and we find a flux limit of ${\lesssim}1.7 \times 10^{-4}\, \mathrm{ph\, cm^{-2}\, s^{-1}}$. We construct spectral models for primordial black hole (PBH) evaporation and annihilation/decay of particle DM, and subsequent annihilation of e+s produced in these processes. We exclude that the totality of DM in Ret II is made of a monochromatic distribution of PBHs of masses ${\lesssim}8 \times 10^{15}\, \mathrm{g}$. Our limits on the velocity-averaged DM annihilation cross section into e+e− are $\langle \sigma v \rangle \lesssim 5 \times 10^{-28} \left(m_{\rm DM} / \mathrm{MeV} \right)^{2.5}\, \mathrm{cm^3\, s^{-1}}$. We conclude that analysing isolated targets in the MeV γ-ray band can set strong bounds on DM properties without multi-year data sets of the entire MW, and encourage follow-up observations of Ret II and other dwarf galaxies.