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Aims This study evaluates the action of Weissella paramesenteroides WpK4 on amoebic colitis. Methods and Results Weissella paramesenteroides WpK4 was administered in Entamoeba dispar infected and noninfected mice and clinical parameters were evaluated. Following 7 days, the caeca were collected for histopathology, morphometry and immunohistochemical staining of MUC‐2, CDC‐47 and IgA. The treatment reduced diarrhoea and the presence of blood in the faeces and diminished the area of necrosis, also causing weight gain. Also, the addition of this bacterium enhanced the expression of the mucin (MUC‐2). The reduction in necrosis and increased CDC‐47 expression indicates significant epithelial regeneration. The negative correlation between CDC‐47 and the necrosis area reveals that the bacterium favoured the recovery of the necrotic regions and the positive correlation found between the expression of MUC‐2 and CDC‐47 indicates that the epithelial regeneration also supports the synthesis of MUC‐2. Conclusions Weissella paramesenteroides WpK4 was able to increase the protection of the intestinal mucosa against experimental amoebic colitis through the increase of MUC‐2 and epithelial regeneration. Significance and Impact of the Study Weissella paramesenteroides WpK4 presents the potential to become a complementary tool in the treatment of amoebic colitis.