Thalictrum maritimum is an endangered, endemic species in East Spain, growing in areas of relatively low salinity in littoral salt marshes. A regression of its populations and the number of individuals has been registered in the last decade. This study aimed at establishing the causes of this reduction using a multidisciplinary approach, including climatic, ecological, physiological and biochemical analyses. The climatic data indicated that there was a direct negative correlation between increased drought, especially during autumn, and the number of individuals censused in the area of study. The susceptibility of this species to water deficit was confirmed by the analysis of growth parameters upon a water deficit treatment applied under controlled greenhouse conditions, with the plants withstanding only 23 days of complete absence of irrigation. On the other hand, increased salinity does not seem to be a risk factor for this species, which behaves as a halophyte, tolerating in controlled treatments salinities much higher than those registered in its natural habitat. The most relevant mechanisms of salt tolerance in T. maritimum appear to be based on the control of ion transport, by (i) the active transport of toxic ions to the aerial parts of the plants at high external salinity—where they are presumably stored in the leaf vacuoles to avoid their deleterious effects in the cytosol, (ii) the maintenance of K+ concentrations in belowground and aboveground organs, despite the increase of Na+ levels, and (iii) the salt-induced accumulation of Ca2+, particularly in stems and leaves. This study provides useful information for the management of the conservation plans of this rare and endangered species.