Anisakis simplex, a nematode from the Anisakidae family, infects various commercially significant fish species, posing public health concerns as humans can become accidental hosts by consuming contaminated fish. The infection, known as anisakiasis, typically presents with gastrointestinal symptoms, including epigastric pain, nausea, and vomiting. In some cases, the larvae penetrate the digestive wall and reach organs such as the liver, pancreas, and lymph nodes, remaining latent until degraded. The life cycle of this parasite involves multiple stages, requiring intermediate hosts such as small planktonic crustaceans and larger marine mammals or fish. Humans typically ingest the third larval stage (L3) by consuming raw or undercooked fish, leading to anisakiasis. Anisakis simplex is also a significant allergen source, causing allergic reactions such as urticaria, angioedema, and anaphylaxis in sensitized individuals. The first report of allergy due to A. simplex was in Japan in the 1990s, and the risk of food allergies from this parasite is notably high in cultures consuming raw fish, like in Peru and Japan. With globalization, the incidence of anisakiasis in developed countries might be underestimated. Fourteen allergens of A. simplex have been officially recognized by the World Health Organization and the International Union of Immunological Societies, with significant cross-reactivity to other allergens like dust mites, wasp venom, and cockroaches. Diagnosis of anisakiasis involves endoscopic visualization of larvae, while serological tests face challenges due to protein cross-reactivity. Innovative diagnostic methods like the basophil activation test have shown high accuracy and specificity. Additionally, the use of purified recombinant and deglycosylated allergens improves diagnostic specificity and sensitivity. The prevalence of allergic diseases, including food allergies, is rising globally, exacerbated by infections like anisakiasis. This zoonotic infection necessitates careful monitoring, especially in societies with high raw fish consumption. The study of Anisakis simplex’s allergens and their cross-reactivity remains crucial for developing effective diagnostic and management strategies.