Excipients have been identified as 'inert' substances that often enhance the non-pharmacological aspects of a medication. However, recent clinical evidence elucidates their potential in inducing anaphylaxis and indicates that they are often overlooked as potential allergens in routine clinical practice. The aim of the study was to assimilate published evidence on excipient-induced allergies associated with the use of oral medications and to underline their potential as potent allergens. A systematic literature search of MEDLINE, EMBASE and International Pharmaceutical Abstracts databases was performed for case reports published from inception to June 2024. Studies were excluded if they were animal and laboratory studies or not published in English, full-text articles were unavailable, and they lacked essential information. This systematic review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Polyethylene glycol was the most prevalent allergenic excipient, followed by colouring agents. Clinical manifestations exhibited wide variability ranging from mild to life-threatening reactions, and the most common presentations were urticaria and angioedema. Most patients recovered spontaneously after withdrawal of the offending agent with less than half necessitating additional drug interventions and only a single instance of reported fatality, which cannot be attributed to the excipient alone. Despite being labelled as inert, excipients pose a significant threat for the development of allergic reactions. Simple measures such as increased awareness among patients and healthcare professionals, comprehensive history taking, reviewing medication compositions and improved patient awareness regarding potentially allergenic excipients can aid in avoiding these readily preventable reactions.