Non-surgical periodontal therapy is often performed as a combinational approach using supplemental systemic amoxicillin and metronidazole. Better clinical outcomes, less need for periodontal surgery and limited systemic complications are arguments to justify such an approach. However, combination therapy with systemic antibiotic treatment is still a matter of debate due to emerging antibiotic resistance patterns. In this case report, a 61-year-old women suffering from an acute pancreatitis following systemic antibiotic combinational treatment as part of a non-surgical periodontal therapy is described. Following adequate symptomatic treatment during a hospitalization of three days, the patient recovered and periodontal conditions improved significantly thereafter. This case report illustrates a rare, but potentially serious complication when prescribing systemic combinational antibiotics in non-surgical periodontal therapy. Adequate history taking and timely diagnosis of pancreatitis if developing is important to provide relevant treatment and to avoid pancreatitis-associated complications.