Intestinal infection with the protozoan parasite Entamoeba histolytica elicits a local immune response with rising of specific secretory IgA (sIgA) antibodies detectable in several compartments associated to mucosa. Anti-amoebic sIgA antibodies have been reported in faeces, saliva, bile and breast milk from dysenteric patients and research trying to elucidate their role in protection has recently intensified. IgA antibodies inhibit the in vitro adherence of E. histolytica trophozoites to epithelial cell monolayers by recognizing several membrane antigens, including the galactose-binding lectin (Gal-lectin), main surface molecule involved in adherence, and the serine and cystein-rich proteins, all of them potential vaccine candidates. In fact, the presence of sIgA anti-Gal lectin in faeces of patients recovered from amoebic liver abscess (ALA) was associated with immunity to E. dispar. Moreover, the combined nasal and intraperitoneal vaccination of C3H/HeJ mice with native and recombinant Gal-lectin protected mice against an intracecal challenge with virulent E. histolytica trophozoites, protection that seemed to be associated with the induction of specific intestinal sIgA antibodies. Therefore, the stimulation of intestinal secretory response by mucosal delivery of amoebic antigens has been positioned as a promising strategy for inducing protection against human amoebiasis.