β-Lactams, particularly penicillins, may cause several allergic reactions. We described symmetric drug-related intertriginous and flexural exanthema (SDRIFE) illness in this case, a rare instance of systemic contact dermatitis caused by amoxicillin/clavulanic acid that needs to be considered in the differential diagnosis. A 65-year-old male patient was admitted to our Allergy Outpatient Clinic because of increased blue-purple pigmentation on the flexural surfaces of the hip, forearm, axilla, and posterior face of the neck. The patient was receiving a combination of angiotensin receptor blocker (ARB) and hydrochlorothiazide diuretic medication for hypertension. The patient used an antibiotic containing amoxicillin three months ago; As a result, there was localized redness, itching, and black spotting without any systemic symptoms. Similarly, the patient reported that when he used amoxicillin for an upper respiratory tract infection eight months ago, he experienced similar side effects within 20 days and recovered when he applied corticosteroid ointment. Due to the symmetrical site involvement following the consumption of penicillin group antibiotics with a five-month gap and subsequent comparable reactions in our patient, SDRIFE was taken into consideration. The results of the skin punch biopsy identified Baboon Syndrome (SDRIFE). Treatment with topical corticosteroids and antihistamines began. Clinically speaking, SDRIFE is distinguished by significant erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal/perigenital area, symmetric involvement of at least one other intertriginous or flexural area, and the absence of systemic signs or symptoms. The possibility that the medication may have contributed to the patient's erythematous eruption in the flexural regions should be taken into account, and the patient should be advised to stop taking the medication and not use it again.