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Immune checkpoint inhibitors and targeted therapies efficiently treat various malignancies and diseases. However, these therapies may precipitate immune-related adverse events and side effects involving the gastrointestinal (GI) tract. Patients present with variable, non-specific findings, leading to diagnostic difficulties. Among these, colitis and diarrhoea are reported as the most common GI side effects, which can limit the use of these treatment regimens. This review aims to highlight the lower GI injuries and toxicities associated with each class of drugs, providing guidance for prompt management to treating physicians, particularly oncologists. We comprehensively reviewed the literature focusing on therapies that are used to treat malignancies, such as inhibitors of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), B-lymphocyte antigen (CD20), tyrosine kinase (TK), proto-oncogene B-Raf (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK). We summarised the clinical, endoscopic and pathological features of each drug. Anti-PD-L1/PD1 and anti-CTLA-4 induced colitis similar to microscopic colitis and inflammatory bowel disease (IBD)-like, and rarely perforation. Anti-CD20 inhibitors were associated with IBD development. TK inhibitors were mostly linked to diarrhoea. GI toxicity with MEK and BRAF inhibitors included diarrhoea, abdominal pain and GI bleeding. This review serves as an accessible reference for oncologists, gastroenterologists and pathologists, aiming to improve patient management and outcomes.