Alpha-gal syndrome (AGS) is an IgE-mediated allergy to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) that can trigger delayed anaphylaxis after exposure to non-primate mammal products. Although its perioperative impact is well described in cardiac surgery, guidance for spine surgery is lacking. We investigated common hemostatic agents, dural substitutes, and grafts used in spine surgery at our institution located in Suffolk County, NY, which has the highest prevalence of AGS nationwide, and classified them as safe or unsafe based on the presence or absence of mammal products. Additionally, we discuss anesthetic considerations and the workup and pretreatment of AGS patients, as well as present an illustrative case of an AGS patient who experienced intraoperative anaphylaxis during a deformity correction surgery A review of 25 commonly used agents showed that 64% were potentially unsafe for AGS patients. In contrast, plant-based polysaccharide powders, oxidized cellulose, human recombinant thrombin, and synthetic dural sealants are safe alternatives. AGS poses unique risks in spine surgery because the use of many hemostatic, graft, and dural-repair agents that contain mammal products is commonplace. A structured pathway that includes preoperative allergy consultation, α-gal IgE testing, pre-medication, pharmacy-verified product lists, and real-time team communication can prevent life-threatening reactions. As AGS incidence rises, spine surgeons must recognize high-risk patients, substitute for safe biomaterials when able, and coordinate perioperative care to avoid anaphylaxis.