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Sodin 5 is a type 1 ribosome-inactivating protein isolated from the seeds of <i>Salsola soda</i> L., an edible halophytic plant that is widespread in southern Europe, close to the coast. This plant, known as ‘agretti’, is under consideration as a new potential crop on saline soils. Considering a possible defence role of sodin 5 in the plant, we report here its antifungal activity against different halophilic and halotolerant fungi. Our results show that sodin 5 at a concentration of 40 µg/mL (1.4 µM) was able to inhibit the growth of the fungi <i>Trimmatostromma salinum</i> (35.3%), <i>Candida parapsilosis</i> (24.4%), <i>Rhodotorula mucilaginosa</i> (18.2%), <i>Aspergillus flavus</i> (12.2%), and <i>Aureobasidium melanogenum</i> (9.1%). The inhibition observed after 72 h was concentration-dependent. On the other hand, very slight growth inhibition was observed in the fungus <i>Hortaea werneckii</i> (4.2%), which commonly inhabits salterns. In addition, sodin 5 showed a cytotoxic effect on the Sf9 insect cell line, decreasing the survival of these cells to 63% at 1.0 µg/mL (34.5 nM). Structural analysis of sodin 5 revealed that its N-terminal amino acid residue is blocked. Using mass spectrometry, sodin 5 was identified as a homologous to type 1 polynucleotide:adenosine glycosylases, commonly known as ribosome-inactivating proteins from the Amaranthaceae family. Twenty-three percent of its primary structure was determined, including the catalytic site.