A comparative analysis of environmental conditions between Alpine and Apennine lakes/ponds which represent different faces of European mountain regions was conducted. The data set was created on the basis of previous works carried out by national and international institutions including biological, physical–chemical, geographic, and precipitation data from 27 lakes/ponds placed at altitudes ranging from 2334 ± 294 m a.s.l. (in the Alps) and 1541 ± 154 m a.s.l. (in the Apennines), with mean maximum depths of about 5.5 ± 4.6 m. A specific focus was dedicated to chironomids as outstanding sentinels for local and global changes in habitat conditions. Species richness and Taxonomic Distinctness Indices were applied to lakes/ponds macroinvertebrates to highlight differences in the biodiversity of the two areas. Subsequently, associations between descriptors of the mountain region climate, lithology, water chemistry, lake morphology, geography, macroinvertebrate assemblage richness, and distinctness were examined through Principal Component Analysis, Analysis of Variance, and Non-metric Multi-dimensional Scaling. Results showed strong positive correlations between mean annual precipitation and temperature with lake macroinvertebrate biodiversity as a whole and with chironomid in particular. Thus, these shore habitats face a threat under climate change conditions (impacting thermal and precipitation regimes). These results are also central in showing that even small ecosystems are important sources of biodiversity for the lower altitudes, stressing the urgency of including them within targeted monitoring and action plans to preserve their peculiar habitat, flora, and fauna.