Introduction: Indolizine (INDO) is a bicyclic heteroaromatic compound containing two fused rings (10 pi-electron system); pyridine and pyrrole via bridging N-atom at the centre of both the rings. This scaffold exists very rarely in nature and is an isomeric form of indole. It is analogous of indole (isoelectrically resembles indole system) which has marked potency in the biological activity. The scaffold is also related to the heterocyclic compound purine which is the base of cellular organisms. The structure of INDO is found in many natural products and is important in the pharmaceutical area because of prominent biological properties. Aims: Highlighting the recent pharmacotherapeutic progress of indolizine-based compounds. Methodology: In the preparation of this review article, a comprehensive scrutiny of the published literature in diverse pharmaceutical and medical databases such as Google Scholar, PubMed, etc. was successfully conducted and classified accordingly. Results: The derivatives of INDO have various applications in drug design, biological area, and pharmaceutical research. INDO is a pharmacological active moiety and broadly displays biological activities such as anti-microbial, hypoglycemic, anti-inflammatory, analgesic, anti-oxidant, anti-depressant, anti-cancer activities, etc. The substituents on the INDO nucleus ring exhibit a wide range of biological activities such as anti-cancer, anti-bacterial, anti-fungal, anti-tubercular, anti-histamine, CNS-depressant activity, etc. Conclusion: This imperative review article broadly highlighted the summary of the diverse pharmacotherapeutic potentials of INDO. This review will be a true inspiration for the medicinal chemists and pharmacologists in designing and screening lowmolecular-weight inhibitors of the INDO scaffold.