This study highlights the decomposing role through the hydrolytic activities of fungi isolated from natural environments represented by brackish and hypersaline lakes in Romania. Novel strains belonging to the Penicillium, Aspergillus, and Emericellopsis genera were isolated and screened for the ability to produce extracellular hydrolytic enzymes, i.e., proteases, lipases, amylases, cellulases, xylanases, and pectinases. According to salt requirements, they were classified as moderate halophilic and halotolerant strains. Agar plate-based assays with Tween 80, slide cultures with organic deposits, and quantitative evaluation allowed the selection of Aspergillus sp. BSL 2-2, Penicillium sp. BSL 3-2, and Emericellopsis sp. MM2 as potentially good decomposers of organic matter not only in lakes but also on deposits covering the mural paintings. Experiments performed on painted experimental models revealed that only Penicillium sp. BSL 3-2 decomposed Paraloid B72, transparent dispersion of casein, beeswax, sunflower oil, and soot. Moreover, using microscopic, spectroscopic, and imaging methods, it was proved the efficiency of Penicillium sp. BSL 3-2 for decomposition of organic deposits artificially applied on frescoes fragments.