BACKGROUND: Alpha-gal syndrome (AGS) is associated with a potentially severe delayed immunoglobulin E-based hypersensitivity reaction produced via transmission of a salivary oligosaccharide (galactose-⍺-1,3-galactose) predominately from the bite of the lone star tick (Amblyomma americanum). Sensitized people are at an increased risk of experiencing cross-reactivity reactions to numerous foods, pharmaceuticals, and medical and dental products that could result in a spectrum of pathophysiological responses, ranging from gastrointestinal and cutaneous disturbances to anaphylaxis. The authors have summarized the relevant literature and presented a case report describing an alpha-gal (AG) reaction associated with oral health care. TYPES OF STUDIES REVIEWED: The authors provided an overview of clinical studies, review articles, case reports, and case series of AGS obtained from PubMed and Google Scholar electronic databases. In addition, various medical and dental pharmaceuticals and health care products were reviewed for the presence of AG epitopes. RESULTS: Factors implicated in an AGS-like event included consuming nonprimate red meat and dairy products, intake of pharmaceuticals with animal-based ingredients and excipients, and use of medical and dental products containing AG epitopes. The most common promoter of AGS-related dental events was the administration of animal-based hemostatic agents. PRACTICAL IMPLICATIONS: Oral health care providers should be knowledgeable about the salient features of AGS and perform a thorough review of an affected patient's diagnosis, triggering events, associated adverse incidents, and therapeutic measures used. To gain greater insight into an affected patient's disorder, consultation with their attending allergist or immunologist is advised. To reduce the onset of a hypersensitivity reaction, attending clinicians must maintain strict avoidance of the use of pharmaceuticals and medical or dental products that express AG epitopes.