This study investigates the role of indole derivatives in mediating host-microbiota interactions and inter-microbial communication. The research focuses on indole-3-lactic acid (ILA), a key molecule produced by *Lactobacillus*, which protects against intestinal inflammation and corrects microbial dysbiosis. ILA increases the expression of enzymes involved in tryptophan metabolism, leading to the synthesis of other indole derivatives such as indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). These indole derivatives mitigate intestinal inflammation and modulate the gut microbiota in both DSS-induced and IL-10−/− spontaneous colitis models. ILA increases the abundance of tryptophan-metabolizing bacteria like *Clostridium* and enhances the production of IPA and IAA. The protective effects of ILA are dependent on the intestinal microbiota, as demonstrated by the failure of mutant *Lactobacillus* strains to protect against inflammation or produce other derivatives. ILA-mediated microbial cross-feeding is microbiota-dependent and enhances indole derivatives production under conditions of dysbiosis induced by *Citrobacter rodentium* or DSS, but not by antibiotic disruption. These findings highlight the mechanisms by which microbiome-host crosstalk cooperatively controls intestinal homeostasis through indole derivatives, providing potential targets for the development of interventions for dysbiosis-driven diseases.This study investigates the role of indole derivatives in mediating host-microbiota interactions and inter-microbial communication. The research focuses on indole-3-lactic acid (ILA), a key molecule produced by *Lactobacillus*, which protects against intestinal inflammation and corrects microbial dysbiosis. ILA increases the expression of enzymes involved in tryptophan metabolism, leading to the synthesis of other indole derivatives such as indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). These indole derivatives mitigate intestinal inflammation and modulate the gut microbiota in both DSS-induced and IL-10−/− spontaneous colitis models. ILA increases the abundance of tryptophan-metabolizing bacteria like *Clostridium* and enhances the production of IPA and IAA. The protective effects of ILA are dependent on the intestinal microbiota, as demonstrated by the failure of mutant *Lactobacillus* strains to protect against inflammation or produce other derivatives. ILA-mediated microbial cross-feeding is microbiota-dependent and enhances indole derivatives production under conditions of dysbiosis induced by *Citrobacter rodentium* or DSS, but not by antibiotic disruption. These findings highlight the mechanisms by which microbiome-host crosstalk cooperatively controls intestinal homeostasis through indole derivatives, providing potential targets for the development of interventions for dysbiosis-driven diseases.