Gastrointestinal (GI) infections are caused by a diverse array of pathogens—including bacteria, viruses, parasites, and fungi—that primarily enter the host via ingestion of contaminated food or water. Upon surviving gastric acidity, these pathogens interact with the intestinal epithelium through virulence mechanisms such as adhesion, colonization, toxin production, invasion, and inflammation. Bacterial agents like Salmonella spp. trigger robust inflammatory responses leading to mucosal damage, while toxins from Vibrio cholerae and Shigella spp. disrupt epithelial integrity, resulting in secretory diarrhea and enteric inflammation. Viral GI pathogens—including Rotavirus, Norovirus, Adenovirus, Astrovirus, and Sapovirus—target enterocytes, impairing absorption and secretion, and manifesting as diarrhea, vomiting, and abdominal pain. Recent advances in molecular diagnostics, such as multiplex PCR panels and metagenomic sequencing, have enhanced pathogen detection and epidemiological surveillance. Parasitic infections, prevalent in tropical and resource-limited settings, are transmitted via fecal-oral routes. Entamoeba histolytica, the causative agent of amoebiasis, invades colonic mucosa, leading to ulceration and systemic dissemination. Improved diagnostic tools—including antigen detection assays and real-time PCR—have refined clinical management. Fungal GI infections, though less common, pose significant risks to immunocompromised individuals. Pathogenesis involves mucosal invasion facilitated by dysbiosis and immune suppression, with symptoms including odynophagia, abdominal pain, and diarrhea. Diagnosis relies on endoscopy, histopathology, culture, and increasingly on molecular and AI-assisted platforms. Therapeutic strategies include oral rehydration therapy, targeted antimicrobials, vaccines, probiotics, and emerging microbiome-based interventions. Understanding the dynamic interplay between pathogen virulence, host immune responses, and gut microbiota is essential for developing precision-based strategies to prevent and manage GI infections.