Studies on microbial adaptations to salt stress, particularly in fungi, have focused mainly on high concentrations of NaCl. The effects of other inorganic salts on biological systems are much less well known. This study investigates the effects of MgCl2 (0-2.0 M), a chaotropic salt, on the halophilic fungus Aspergillus sydowii (EXF-12860) and compares these results with those obtained with the kosmotropic NaCl. While A. sydowii thrived at MgCl2 concentrations previously considered lethal (up to 2.0 M), differences in morphological, physiological, metabolic, and molecular responses were observed. At 0.5-1.0 M, growth rates were similar under both salts, but higher MgCl2 concentrations (1.5-2.0 M) significantly inhibited growth, reduced hyphal elongation, and decreased cell density. During growth in the presence of NaCl, a wide range of carbon sources was utilized, but high MgCl2 interfered with substrate metabolism and uncoupled growth from metabolic activity. Both salts induced the production of compatible solutes (glycerol, erythritol), with higher accumulation under MgCl2. Oxidative stress responses were also stronger under MgCl2, including increased catalase and glutathione peroxidase activity. Transcriptomic analyses revealed significant changes in gene expression under MgCl2 stress, with upregulation of ion transport, cell wall remodelling, glycerol biosynthesis, and oxidative defense pathways. In contrast, NaCl triggered responses focused on osmotic balance and maintenance of cell integrity. These findings emphasize the need for a deeper investigation of microbial tolerance mechanisms in chaotropic environments.