The first step of ice-sheet build-up on Antarctica at the Eocene-Oligocene boundary was followed by a phase of climate instability culminating during the Miocene with a warming event called the Middle Miocene Climate Optimum (MMCO), that ended with a marked cooling phase identified as the Middle Miocene Climate Transition (MMCT). While numerous benthic foraminifera δ18O and Mg/Ca data have been used to capture the global climate evolution during this interval of climate and ice-sheet instability, geochemical records from shallow-water carbonates still remain scarce. Yet such records are crucial to capture the diversity of regional environmental responses to global climate changes, and thus to better understand the behavior of our climate system during this critical interval. In this work, we test the potential of a multi-proxy approach (δ18O, clumped isotope (Δ47), strontium isotopes (87Sr/86Sr)) applied to bivalves recovered from the Liguro-Provencal Basin and Rhodano-Provencal basin (Northwestern of the Mediterranean Sea) to reconstruct the evolution of shallow seawater temperature and salinity in this region over the latest Oligocene to Middle Miocene interval (~10 Myrs). Our results highlight a local cooling in the northwestern Mediterranean Sea during the MMCO that contrasts with the warming observed in other regions, with seawater temperatures inferred from Δ47 analyses in the 13–18 °C range. These cool seawater temperatures recorded in the studied region during the MMCO are much cooler than those recorded in the open oceans, but are in agreement with the proliferation of bryozoan observed in the Castillon-Du-Gard area during this interval. Low bivalve δ18O values (−3.24‰ in average) are recorded during this episode are interpreted to reflect enhanced freshwater inputs, lowering local salinity and seawater δ18O. Such enhanced freshwater inputs point to a phase of enhanced hydrological cycle in the studied region, possibly linked to the global mid-Miocene warming event. Bivalve 87Sr/86Sr data mostly fall within the global seawater Sr isotope reference curve, but remain compatible with enhanced freshwater inputs during the Aquitanian and during the Langhian, as these inputs were probably not important enough to induce a large departure from the seawater curve at a regional scale.