The seagrass Posidonia oceanica forms extensive meadows in the Mediterranean Sea. Studies on their associated highly diverse invertebrate assemblages are limited to the western Mediterranean. The eastern Mediterranean, however, is a basin undergoing rapid change due to the synergistic effects of climate warming, biological invasions and other human stressors that are driving native biodiversity to regional-scale collapses. We here surveyed the shelled molluscan assemblage of a Posidonia oceanica meadow in Plakias, south-western Crete, the first such study in the eastern Mediterranean Sea. This area has increased its yearly mean temperature by 1 °C in the last 20 years and is under heavy pressure by Lessepsian species. We sampled across a 5- to 20-m depth gradient, in two seasons to capture intra-annual variation and the leaf and rhizome strata separately. Against our expectations, the molluscan assemblage proved to be highly diverse, with species richness, dominant species and trophic guilds comparable to healthy western Mediterranean ones, and with a negligible non-indigenous component. The diversity of the native community (following the biotic resistance hypothesis) and oxygen supersaturation in the meadow may cause greater resistance to biological invasions and warming, respectively, suggesting that Posidonia oceanica meadows may act as a precious refugium for native biodiversity in the fast changing eastern Mediterranean Sea.