Infections caused by the protozoans Entamoeba histolytica (E. histolytica), Giardia lamblia (G. lamblia), and Trichomonas vaginalis (T. vaginalis) represent a global public health concern. Albendazole and mebendazole are drugs used to treat parasitosis resulting from protozoa. However, the low aqueous solubility of these compounds has led to the exploration of new strategies to enhance their solubility, with the formation of salts being a commonly employed strategy. The sulfonates A1, A2, and A3 of albendazole, and M1, M2, and M3 of mebendazole were synthesized, and their antiparasitic activity was determined in vitro against trophozoites of E. histolytica, G. lamblia, and T. vaginalis. Consequently, IC50 values ranged from 24.17 to 138.02 µM for the albendazole and mebendazole salts. For comparison, the IC50 values for the positive controls—albendazole, mebendazole, and metronidazole—ranged from 16.08 to 270.66 µM. Additionally, it was determined that salts A1, A3, M2, and M3 do not exhibit cytotoxic effects at concentrations of 500 µM on the VERO cell line. Taken together, these findings indicate that the formation of these new solid saline phases enhances the antiparasitic effects in vitro, which is crucial in the current search for improved, safe, and effective antiparasitic agents.